Dr F. Javier Salguero

Research Interests

Javier's main research interest is host-pathogen interactions and the basis of immune response against pathogens. The long-term objective of his research is to gain further insight into the understanding of the changes induced in the animal host after infection, by using experimental animal models, with special interest in transboundary and emerging diseases, principally Porcine Reproductive and Respiratory Syndrome in pigs and Mycobacterium spp. infection in cattle and wildlife species. Javier is also interested in the application of novel techniques to study the changes in the host after infection, such as laser-capture microdissection linked to qPCR and RNAseq and other molecular biology techniques. As a qualified veterinary pathologist, the investigation of the aetiology and pathogenesis of spontaneous diseases are always a nice challenge to accept. A true believer in the 3Rs, Javier is very interested in the development of animal and human disease models.

Teaching

Veterinary Biosciences BSc (Hons)

  • Veterinary Anatomy and Animal Handling (BMS1028)
  • Veterinary Immunology and Pathology (BMS3062)
  • Animal Infectious Diseases and Veterinary Public Health (BMS3074)

Veterinary Medicine & Science BVMSci

  • Structure and Function - Cells and Genes in Context (VMS1003)
  • Structure and Function - Integument and Alimentary (VMS1004)
  • Structure and Function - Cardiovascular, Respiratory and Musculoskeletal Systems (VMS1005)
  • Structure and Function - Neurological and Haemopoietic Systems (VMS1006)
  • Structure and Function - Urinary and Reproductive Systems (VMS1007)

Veterinary Microbiology MSc

  • Diseases of Animal Systems: Gastro-intestinal Diseases of Animals (MMVM007). Module Coordinator
  • Diseases of Animal Systems: CNS and Skin Diseases of Animals (MMVM010)

Departmental Duties

Member of the Veterinary Pathology Diagnostic Group

Affiliations

Fellow of the Royal College of Pathologists

Diplomate of the European College of Porcine Health Management

Member of the European Society of Veterinary Pathology

Member of the European Association of Porcine Health Management

Member of the Spanish Society of Laboratory Animal Science within FELASA

Member of the Spanish Society of Veterinary Anatomic Pathology 

Member of the Editorial Board of the Journal of Medical Microbiology Case Reports

Associate Editor (Pathology) of Frontiers in Veterinary Science

Contact Me

E-mail:
Phone: 01483 68 9872

Find me on campus
Room: 01 VSM 02


My office hours

Monday to Friday 9.30 - 18.00, by appointment only

Publications

Highlights

  • Conejero L, Potempa K, Graham CM, Spink N, Blankley S, Salguero FJ, Panka-Sranujit R, Khaenam P, Banchereau JF, Pascual V, Chaussabe D, Lertmemongkochai G, O'Garra A, Bancroft GJ. (2015) 'The Blood Transcriptome of Experimental Melioidosis Reflects Disease Severity and Shows Considerable Similarity with the Human Disease'. AMER ASSOC IMMUNOLOGISTS JOURNAL OF IMMUNOLOGY, 195 (7), pp. 3248-3261.
  • Smither SJ, Nelson M, Eastaugh L, Nunez A, Salguero FJ, Lever MS. (2015) 'Experimental Respiratory Infection of Marmosets (Callithrix jacchus) With Ebola Virus Kikwit'. OXFORD UNIV PRESS INC JOURNAL OF INFECTIOUS DISEASES, 212, pp. S336-S345.
  • Salguero FJ, Frossard JP, Rebel JM, Stadejek T, Morgan SB, Graham SP, Steinbach F. (2015) 'Host-pathogen interactions during porcine reproductive and respiratory syndrome virus 1 infection of piglets.'. Virus Res, Netherlands: 202, pp. 135-143.
  • García-Nicolás O, Rosales RS, Pallarés FJ, Risco D, Quereda JJ, Graham SP, Frossard JP, Morgan SB, Steinbach F, Drew TW, Strickland TS, Salguero FJ. (2015) 'Comparative analysis of cytokine transcript profiles within mediastinal lymph node compartments of pigs after infection with porcine reproductive and respiratory syndrome genotype 1 strains differing in pathogenicity'. Veterinary Research, 46 (1)
  • Morgan SB, Frossard JP, Pallares FJ, Gough J, Stadejek T, Graham SP, Steinbach F, Drew TW, Salguero FJ. (2014) 'Pathology and Virus Distribution in the Lung and Lymphoid Tissues of Pigs Experimentally Inoculated with Three Distinct Type 1 PRRS Virus Isolates of Varying Pathogenicity.'. Transbound Emerg Dis, Germany: 63 (3), pp. 285-295.
  • Smither SJ, Nelson M, Eastaugh L, Laws TR, Taylor C, Smith SA, Salguero FJ, Lever MS. (2013) 'Experimental respiratory Marburg virus haemorrhagic fever infection in the common marmoset (Callithrix jacchus)'. International Journal of Experimental Pathology, 94 (2), pp. 156-168.
  • Aranday-Cortes E, Bull NC, Villarreal-Ramos B, Gough J, Hicks D, Ortiz-Peláez A, Vordermeier HM, Salguero FJ. (2012) 'Upregulation of IL-17A, CXCL9 and CXCL10 in Early-Stage Granulomas Induced by Mycobacterium bovis in Cattle'. Transboundary and Emerging Diseases, 60 (6), pp. 525-537.
  • Lever MS, Piercy TJ, Steward JA, Eastaugh L, Smither SJ, Taylor C, Salguero FJ, Phillpotts RJ. (2012) 'Lethality and pathogenesis of airborne infection with filoviruses in A129 α/β -/- interferon receptor-deficient mice'. Journal of Medical Microbiology, 61 (1), pp. 8-15.
  • Salguero FJ, Sánchez-Cordón PJ, Núñez A, Fernández de Marco M, Gómez-Villamandos JC. (2005) 'Proinflammatory cytokines induce lymphocyte apoptosis in acute African swine fever infection.'. J Comp Pathol, England: 132 (4), pp. 289-302.

Journal articles

  • Vallejo R, García Marín J, Juste R, Muñoz-Mendoza M, Salguero Bodes F, Balseiro A. (2018) 'Immunohistochemical characterization of tuberculous lesions in sheep naturally infected with Mycobacterium bovis'. BioMed Central BMC Veterinary Research, 14 (154), pp. 1-7.

    Abstract

    Background: Sheep have been traditionally considered as less susceptible to Mycobacterium bovis (Mbovis) infection than other domestic ruminants such as cattle and goats. However, there is increasing evidence for the role of this species as a domestic Mbovis reservoir, mostly when sheep share grazing fields with infected cattle and goats. Nevertheless, there is a lack of information about the pathogenesis and the immune response of Mbovis infection in sheep. The goals of this study were to characterize the granuloma stages produced by the natural infection of Mbovis in sheep, to compare them with other species and to identify possible differences in the sheep immune response. Samples from bronchial lymph nodes from twelve Mbovis-naturally infected sheep were used. Four immunohistochemical protocols for the specific detection of T-lymphocytes, B-lymphocytes, plasma cells and macrophages were performed to study the local immune reaction within the granulomas.

    Results: Differences were observed in the predominant cell type present in each type of granuloma, as well as differences and similarities with the development of tuberculous granulomas in other species. Very low numbers of T-lymphocytes were observed in all granuloma types indicating that specific cellular immune response mediated by T-cells might not be of much importance in sheep in the early stages of infection, when macrophages are the predominant cell type within lesions. Plasma cells and mainly B lymphocytes increased considerably as the granuloma developed being attracted to the lesions in a shift towards a Th2 response against the increasing amounts of mycobacteria. Therefore, we have proposed that the granulomas could be defined as initial, developed and terminal.

    Conclusions: Results showed that the study of the lymphoid tissue granulomata reinforces the view that the three different types of granuloma represent stages of lesion progression and suggest an explanation to the higher resistance of sheep based on a higher effective innate immune response to control tuberculosis infection.

  • Holzer B, Morgan S, Matsuoka Y, Edmans M, Salguero Bodes F, Everett H, Brookes S, Porter E, MacLoughlin R, Charleston B, Subbarao K, Townsend A, Tchilian E. (2018) 'Comparison of heterosubtypic protection in ferrets and pigs induced by a single cycle influenza vaccine'. American Association of Immunologists Journal of Immunology, 200 (12), pp. 4068-4077.

    Abstract

    Influenza is a major health threat, and a broadly protective influenza vaccine would be a significant advance. Signal Minus FLU (S-FLU) is a candidate broadly protective influenza vaccine that is limited to a single cycle of replication, which induces a strong cross-reactive T cell response but a minimal Ab response to hemagglutinin after intranasal or aerosol administration. We tested whether an H3N2 S-FLU can protect pigs and ferrets from heterosubtypic H1N1 influenza challenge. Aerosol administration of S-FLU to pigs induced lung tissue-resident memory T cells and reduced lung pathology but not the viral load. In contrast, in ferrets, S-FLU reduced viral replication and aerosol transmission. Our data show that S-FLU has different protective efficacy in pigs and ferrets, and that in the absence of Ab, lung T cell immunity can reduce disease severity without reducing challenge viral replication.

  • Morgan S, Holzer B, Hemmink J, Salguero Bodes F, Schwartz J, Agatic G, Cameroni E, Guarino B, Porter E, Rijal P, Townsend A, Charleston B, Corti D, Tchilian E. (2018) 'Therapeutic administration of broadly neutralizing FI6 antibody reveals lack of interaction between human IgG1 and pig Fc receptors'. Frontiers Media Frontiers in Immunology, 9 Article number 865

    Abstract

    Influenza virus infection is a significant global health threat. Because of the lack of cross protective universal vaccines, short time window during which antivirals are effective and drug resistance, new therapeutic anti-influenza strategies are required. Broadly cross-protective antibodies that target conserved sites in the hemagglutinin (HA) stem region, have been proposed as therapeutic agents. FI6 is the first proven such monoclonal antibody to bind to H1-H16 and is protective in mice and ferrets. Multiple studies have shown that Fc-dependent mechanisms are essential for FI6 in vivo efficacy. Here we show that therapeutic administration of FI6 either intravenously or by aerosol to pigs did not reduce viral load in nasal swabs or broncho-alveolar lavage, but aerosol delivery of FI6 reduced gross pathology significantly. We demonstrate that pig Fc receptors do not bind human IgG1 and that FI6 did not mediate antibody dependent cytotoxicity (ADCC) with pig PBMC, confirming that ADCC is an important mechanism of protection by anti-stem antibodies in vivo. Enhanced respiratory disease, which has been associated in pigs with cross-reactive non-neutralising anti-HA antibodies, did not occur after FI6 administration. Our results also show that in vitro neutralizing antibody responses are not a robust correlate of protection for the control of influenza infection and pathology in a natural host model.

  • Ashpitel H, Dabbs E, Nemchand J, La Ragione R, Salguero Bodes F, Whiteley M. (2018) 'Histological and Immunofluorescent Analysis of a Large Tributary of the Great Saphenous Vein Treated with a 1920 nm Endovenous Laser: Preliminary Findings'. Elsevier EJVES Short Reports, 39, pp. 7-11.

    Abstract

    Objectives: To analyse the biological effects of a 1920 nm endovenous laser (EVL) on extra-fascial great saphenous vein (GSV) in vitro.

    Methods: A 10 cm length of a large tributary bypassing a hypoplastic segment of the GSV (sometimes called an “extra-fascial GSV”) was obtained during routine varicose vein surgery. The length was treated in five sections with different LEEDs (0 (control), 20, 40, 60, and 80 J/cm) with a 1920 nm EVL at 4W power, in a novel in vitro treatment model. The biological effects were assessed by histological staining of the samples for haematoxylin and eosin (HE) and Martius Scarlet Blue (MSB), and by immunofluorescent detection of p-p53 and VCAM-1.

    Results: Histological analysis showed significant structural damage at LEEDs above 60 J/cm, especially in the intima and media, with the treatment at 80 J/cm causing perforation of the vein wall. In addition, there was a significant increase in p-p53 expression in treated tissue at 60 and 80 J/cm.

    Conclusions: Using this ex vivo model, the results indicate that in vitro treatment with a 1920 nm EVL, at or above an LEED of 60 J/cm and 4 W power, causes significant vein wall cell death reaching deep into the media by a combination of direct thermal damage and apoptosis. A wavelength of 1920 nm appears to be effective for the endovenous ablation of truncal veins.

  • Spanos C, Maldonado E, Fisher C, Leenutaphong P, Oviedo-Orta E, Windridge D, Salguero Bodes F, Bermúdez-Fajardo A, Weeks M, Evans C, Corfe B, Rabbani N, Thornalley P, Miller M, Wang H, Dillon J, Quaglia A, Dhawan A, Fitzpatrick E, Moore J. (2018) 'Proteomic identification and characterization of hepatic glyoxalase 1 dysregulation in non-alcoholic fatty liver disease'. BioMed Central Proteome Science, 16 (4)

    Abstract

    Background: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. However its molecular pathogenesis is incompletely characterized and clinical biomarkers remain scarce. The aims of these experiments were to identify and characterize liver protein alterations in an animal model of NAFLD and to assess novel candidate biomarkers in NAFLD patients. Methods: Liver membrane and cytosolic protein fractions from high fat fed apolipoprotein E knockout (ApoE-/-) animals were analyzed by quantitative proteomics, utilizing isobaric tags for relative and absolute quantitation (iTRAQ) combined with nano-liquid chromatography and tandem mass spectrometry (nLC-MS/MS). Differential protein expression was confirmed independently by immunoblotting and immunohistochemistry in both murine tissue and biopsies from paediatric NAFLD patients. Candidate biomarkers were analyzed by enzyme-linked immunosorbent assay in serum from adult NAFLD patients. Results: Through proteomic profiling, we identified decreased expression of hepatic glyoxalase 1 (GLO1) in a murine model of NAFLD. GLO1 protein expression was also found altered in tissue biopsies from paediatric NAFLD patients. In vitro experiments demonstrated that, in response to lipid loading in hepatocytes, GLO1 is first hyperacetylated then ubiquitinylated and degraded, leading to an increase in reactive methylglyoxal. In a cohort of 59 biopsy-confirmed adult NAFLD patients, increased serum levels of the primary methylglyoxal-derived advanced glycation endproduct, hydroimidazolone (MG-H1) were significantly correlated with body mass index (r=0.520, p<0.0001). Conclusions: Collectively these results demonstrate the dysregulation of GLO1 in NAFLD and implicate the acetylation-ubquitination degradation pathway as the functional mechanism. Further investigation of the role of GLO1 in the molecular pathogenesis of NAFLD is warranted.

  • Rusbridge C, Salguero Bodes F, David M, Faller K, Bras J, Guerreiro R, Richard-Loendt A, Grainger D, Head E, Brandner S, Summers B, Hardy J, Tayebi M. (2018) 'An aged canid with behavioural deficits exhibits blood and cerebrospinal fluid amyloid beta oligomers'. Frontiers Media Frontiers in Aging Neuroscience, 10 Article number 7 , pp. 1-8.

    Abstract

    Many of the molecular and pathological features associated with human Alzheimer disease (AD) are mirrored in the naturally occurring age-associated neuropathology in the canine species. In aged dogs with declining learned behaviour and memory the severity of cognitive dysfunction parallels the progressive build up and location of Aβ in the brain. The main aim of this work was to study the biological behaviour of soluble oligomers isolated from an aged dog with cognitive dysfunction through investigating their interaction with a human cell line and synthetic Aβ peptides. We report that soluble oligomers were specifically detected in the dog’s blood and cerebrospinal fluid via anti-oligomer- and anti-Aβ specific binders. Importantly, our results reveal the potent neurotoxic effects of the dog’s cerebrospinal fluid on cell viability and the seeding efficiency of the cerebrospinal fluid-borne soluble oligomers on the thermodynamic activity and the aggregation kinetics of synthetic human Aβ. The value of further characterising the naturally occurring Alzheimer-like neuropathology in dogs using genetic and molecular tools is discussed.

  • Villarreal-Ramos B, Berg S, Whelan A, Holbert S, Carreras F, Salguero Bodes F, Khatri B, Malone K, Rue-Albrecht K, Shaughnessy R, Smyth A, Ameni G, Aseffa A, Sarradin P, Winter N, Vordermeier M, Gordon S. (2018) 'Experimental infection of cattle with Mycobacterium tuberculosis isolates shows the attenuation of the human tubercle bacillus for cattle'. Nature Publishing Group Scientific Reports, 8 Article number 894

    Abstract

    The Mycobacterium tuberculosis complex (MTBC) is the collective term given to the group of bacteria that cause tuberculosis (TB) in mammals. It has been reported that M. tuberculosis H37Rv, a standard reference MTBC strain, is attenuated in cattle compared to Mycobacterium bovis. However, as M. tuberculosis H37Rv was isolated in the early 1930s, and genetic variants are known to exist, we sought to revisit this question of attenuation of M. tuberculosis for cattle by performing a bovine experimental infection with a recent M. tuberculosis isolate. Here we report infection of cattle using M. bovis AF2122/97, M. tuberculosis H37Rv, and M. tuberculosis BTB1558, the latter isolated in 2008 during a TB surveillance project in Ethiopian cattle. We show that both M. tuberculosis strains caused reduced gross and histopathology in cattle compared to M. bovis. Using M. tuberculosis H37Rv and M. bovis AF2122/97 as the extremes in terms of infection outcome, we used RNA-Seq analysis to explore differences in the peripheral response to infection as a route to identify biomarkers of progressive disease in contrast to a more quiescent, latent infection. Our work shows the attenuation of M. tuberculosis strains for cattle, and emphasizes the potential of the bovine model as a ‘One Health’ approach to inform human TB biomarker development and post-exposure vaccine development.

  • Stakaitytė G, Nwogu N, Dobson S, Knight L, Wasson C, Salguero Bodes F, Blackbourn D, Blair G, Mankouri J, Macdonald A, Whitehouse A. (2017) 'Merkel cell polyomavirus small T antigen drives cell motility via Rho-GTPase-induced filopodia formation'. American Society for Microbiology Journal of Virology, 92 (2) Article number e00940-17 , pp. 1-21.

    Abstract

    Cell motility and migration is a complex, multi-step, and multi-component process, intrinsic to progression and metastasis. Motility is dependent on the activity of integrin receptors and Rho-family GTPases resulting in the remodelling of the actin cytoskeleton and formation of various motile actin-based protrusions. Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high likelihood of recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is associated with the majority of MCC cases, and MCPyV-induced tumourigenesis largely depends on the expression of the small tumour antigen (ST). Since the discovery of MCPyV, a number of mechanisms have been suggested to account for replication and tumourigenesis, but to date, little is known about potential links between MCPyV T antigen expression and the metastatic nature of MCC. Previously, we have described the action of MCPyV ST on the microtubule network and how this impacts on cell motility and migration. Here we demonstrate that MCPyV ST affects the actin cytoskeleton, to promote the formation of filopodia, through a mechanism involving the catalytic subunit of protein phosphatase 4 (PP4C). We also show that MCPyV ST-induced cell motility is dependent upon the activity of Rho-family GTPases Cdc42 and RhoA. In addition, our results indicate that the MCPyV ST-PP4C interaction results in the dephosphorylation of β1 integrin, likely driving the cell motility pathway. These findings describe a novel mechanism by which a tumour virus induces cell motility, which may ultimately lead to cancer metastasis and provides opportunities and strategies for targeted interventions for disseminated MCC.

  • Amarilla S, Gómez-Laguna J, Carrasco L, Rodríguez-Gómez I, Caridad y Ocerín J, Graham S, Frossard J, Steinbach F, Salguero Bodes F. (2017) 'Porcine reproductive and respiratory syndrome type 1 viruses induce hypoplasia of erythroid cells and myeloid cell hyperplasia in the bone marrow of experimentally infected piglets independently of the viral load and virulence'. Elsevier Veterinary Microbiology, 201, pp. 126-135.

    Abstract

    Porcine reproductive and respiratory syndrome viruses (PRRSV) present a wide phenotypic and genetic diversity. Experimental infections have demonstrated viral replication, including highly pathogenic strains (HP-PRRSV), in primary lymphoid organs such as the thymus. However, studies of the bone marrow are scarce but necessary to help elucidate the immunobiology of PRRSV strains of differing virulence. In this study, whereas viral RNA was detected within the bone marrow of animals experimentally infected with both low virulent Lelystad (LV) and 215-06 PRRSV-1 strains and with the highly virulent SU1-bel strain, PRRSV positive cells were only occasionally detected in one SU1-bel infected animal. PRRSV RNA levels were associated to circulating virus with the highest levels detected in LV-infected pigs. At 3 dpi, a decrease in the proportion of haematopoietic tissue and number of erythroid cells in all infected groups was associated with an increase in TUNEL or cleaved caspase 3 labelling and higher counts of myeloid cells compared to control. The expression of IL-1α and IL-6 was elevated at the beginning of the infection in all infected animals. The expression of TNF-α was increased at the end of the study in all infected groups with respect to control. Different PRRSV-1 strains induced, presummably by indirect mechanisms and independently of viral load and strain virulence, moderate and sustained hypoplasia of erythroid cells and myeloid cell hyperplasia at early stages of infection. These changes were paralleled by a peak in the local expression of IL-1α, IL-6 and TNF-α in all infected groups.

  • García-Jiménez W, Salguero Bodes F, D’Elia R. (2017) 'Histopathological and immunohistochemical characterisation of Burkholderia pseudomallei lesions in an acute model of infection with BALB/c mice'. Wiley International Journal of Experimental Pathology, 98 (6), pp. 347-355.

    Abstract

    Organ tissue damage is a key contributor to host morbidity and mortality following infection with microbial agents. Severe immune responses, excessive cellular recruitment and necrosis of cells all play a role in disease pathology. Understanding the pathogenesis of disease can aid in identifying potential new therapeutic targets or simply act as a diagnostic tool. Burkholderia pseudomallei is a gram-negative bacterium that can cause acute and chronic diseases. The BALB/c mouse has been shown to be highly susceptible to aerosol challenge with B. pseudomallei and hence acts as a good model to study the acute and potentially lethal form of the disease melioidosis. In our study, BALB/c mice were challenged and culled at pre-determined time points to generate a pathological time course of infection. Lung, liver and spleen were subjected to pathological and immunohistochemical analysis. The number and type of microscopic lesions within each organ, as well as the location and the mean percentage of neutrophils, B cells, T cells and Burkholderia capsule antigen within the lesions were all characterised during the time course. Neutrophils were determined as the key player in tissue pathology and generation of lesions, with B cells playing an insignificant role. This detailed pathological assessment increases our understanding of B. pseudomallei disease.

  • Salguero Bodes F, Garcia-Jimenez W, Lima I, Seifert K. (2017) 'Histopathological and immunohistochemical characterisation of hepatic granulomas in Leishmania donovani-infected BALB/c mice: a time-course study'. BioMed Central Ltd Parasites and Vectors, 11 (73)

    Abstract

    Background: Visceral leishmaniasis (VL) is a neglected tropical disease (NTD), caused by the intracellular protozoan parasites Leishmania donovani and Leishmania infantum. Symptomatic VL is considered fatal when left untreated. At present, there is no effective vaccine licensed for human use and available chemotherapies have limitations. Understanding the local immune mechanisms required for the control of infection is a key factor for developing effective vaccines and therapeutics.

    Methods: We have investigated the development of the typical granulomatous lesions in the liver in experimental VL over time, together with the local immune responses. BALB/c mice were infected intravenously with a dose of 2 × 107 L. donovani amastigotes (MHOM/ET/67/HU3) and sacrificed at 15, 35 and 63 days post-infection (dpi). Histopathology and immunohistochemical techniques were used for the detection of Leishmania antigen, selected cell types including B and T lymphocytes, macrophages and neutrophils (CD45R-B220+, CD3+, F4/80+ and Ly-6G+) and iNOS.

    Results: Granulomatous lesions were identified as early as 15 dpi in the livers of all infected animals. Three categories were used to classify liver granulomas (immature, mature and clear). Clear granulomas were exclusively detected from 35 dpi onwards. Kupffer cells (F4/80+) were predominant in immature granulomas, regardless of the dpi. Nonetheless, the highest expression was found 63 dpi. Positive staining for iNOS was mainly observed in the cytoplasm of fused Kupffer cells and the highest expression observed at 35 dpi. T cells (CD3+) and B cells (CD45R-B220+) were predominant in more advanced granuloma stages, probably related to the establishment of acquired immunity. Neutrophils (Ly-6G+) were predominantly observed in mature granulomas with the highest expression at 15 dpi. Neutrophils were lower in numbers compared to other cell types, particularly at later time points.

    Conclusions: Our results reflect the role of macrophages during the early stage of infection and the establishment of a lymphocytic response to control the infection in more advanced stages.

  • Chambers M, Aldwell F, Williams G, Palmer S, Gowtage S, Ashford R, Dalley D, Davé D, Weyer U, Salguero Bodes FJ, Nunez A, Nadian A, Crawshaw T, Corner L, Lesellier S. (2017) 'The effect of oral vaccination with Mycobacterium bovis BCG on the development of tuberculosis in captive European badgers (Meles meles)'. Frontiers Media Frontiers in cellular and infection microbiology, 7 (6)

    Abstract

    The European badger (Meles meles) is a reservoir host of Mycobacterium bovis and responsible for a proportion of the tuberculosis (TB) cases seen in cattle in the United Kingdom and Republic of Ireland. An injectable preparation of the bacillus Calmette-Guérin (BCG) vaccine is licensed for use in badgers in the UK and its use forms part of the bovine TB eradication plans of England and Wales. However, there are practical limitations to the widespread application of an injectable vaccine for badgers and a research priority is the development of an oral vaccine deliverable to badgers in bait. Previous studies reported the successful vaccination of badgers with oral preparations of 108 colony forming units (CFU) of both Pasteur and Danish strains of BCG contained within a lipid matrix composed of triglycerides of fatty acids. Protection against TB in these studies was expressed as a reduction in the number and apparent progression of visible lesions, and reductions in the bacterial load and dissemination of infection. To reduce the cost of an oral vaccine and reduce the potential for environmental contamination with BCG, it is necessary to define the minimal efficacious dose of oral BCG for badgers. The objectives of the two studies reported here were to compare the efficacy of BCG Danish strain in a lipid matrix with unformulated BCG given orally, and to evaluate the efficacy of BCG Danish in a lipid matrix at a ten-fold lower dose than previously evaluated in badgers. In the first study, both BCG unformulated and in a lipid matrix reduced the number and apparent progression of visible lesions and the dissemination of infection from the lung. In the second study, vaccination with BCG in the lipid matrix at a ten-fold lower dose produced a similar outcome, but with greater intra-group variability than seen with the higher dose in the first study. Further research is needed before we are able to recommend a final dose of BCG for oral vaccination of badgers against TB or to know whether oral vaccination of wild badgers with BCG will significantly reduce transmission of the disease.

  • Hemmink JD, Morgan SB, Aramouni M, Everett H, Salguero Bodes FJ, Canini L, Porter E, Chase‑Topping M, Beck K, Mac Loughlin R, Carr BV, Brown IH, Bailey M, Woolhouse M, Brookes SM, Charleston B, Tchilian E. (2016) 'Distinct immune responses and virus shedding in pigs following aerosol, intra-nasal and contact infection with pandemic swine influenza A virus, A(H1N1)09'. BioMed Central BMC Veterinary Research, 47 (103)
  • Salguero Bodes F, Gibson S, Garcia-Jimenez W, Gough J, Strickland T, Vordermeier H, Villarreal-Ramos B. (2016) 'Differential cell composition and cytokine expression within lymph node granulomas from BCG vaccinated and non-vaccinated cattle experimentally infected with Mycobacterium bovis'. Wiley Transboundary and Emerging Diseases, 64 (6), pp. 1734-1749.

    Abstract

    Cattle vaccination against bovine tuberculosis (bTB) has been proposed as a supplementary method to help control the incidences of this disease. Bacillus Calmette-Guérin (BCG) is currently the only viable candidate vaccine for immunisation of cattle against bTB, caused by Mycobacterium bovis (M. bovis). In an attempt to characterise the differences in the immune response following M. bovis infection between BCG vaccinated and non-vaccinated animals, a combination of gross pathology, histopathology and immunohistochemical (IHC) analyses was used. BCG vaccination was found to significantly reduce the number of gross and microscopic lesions present within the lungs and lymph nodes. Additionally, the microscopically visible bacterial load of stage III and IV granulomas was reduced. IHC using cell surfaces markers revealed the number of CD68+ (macrophages), CD3+ (T-lymphocytes) and WC1+ cells (γδ T-cells) to be significantly reduced in lymph node granulomas of BCG vaccinated animals, when compared to non-vaccinated animals. B lymphocytes (CD79a+) were significantly increased in BCG-vaccinated cattle for granulomas at stages II, III and IV. IHC staining for iNOS showed a higher expression in granulomas from BCG vaccinated animals compared to non-vaccinated animals for all stages, being statistically significant in stages I and IV. TGFβ expression decreased alongside the granuloma development in non-vaccinated animals, whereas BCG vaccinated animals showed a slight increase alongside lesion progression. IHC analysis of the cytokines IFN-γ and TNFα demonstrated significantly increased expression within the lymph node granulomas of BCG vaccinated cattle. This is suggestive of a protective role for IFNγ and TNFα in the response to M. bovis infection. Findings shown in this study suggest that the use of BCG vaccine, can reduce the number and severity of lesions , induce a different phenotypic response and increase the local expression of key cytokines related to protection.

  • Amarilla S, Gomez-Laguna J, Carrasco L, Rodriguez-Gomez I, Ocerin J, Graham SP, Frossard J, Steinbach F, Salguero Bodes FJ. (2016) 'Thymic depletion of lymphocytes is associated with the virulence of PRRSV-1 strains'. Elsevier Veterinary Microbiology, 188, pp. 47-58.

    Abstract

    Porcine reproductive and respiratory syndrome virus (PRRSV) exists as two distinct viruses, type 1 (PRRSV-1) and type 2 (PRRSV-2). Atrophy of the thymus in PRRSV-2 infected piglets has been associated with a loss of thymocytes. The present study aimed to evaluate the impact of PRRSV-1 strains of differing virulence on the thymus of infected piglets by analysing the histomorphometry, the presence of apoptotic cells and cells producing cytokines. Thymic samples were taken from animals experimentally infected (with LV, SU1-bel, and 215-06 strains) or mock inoculated animals at 3, 7 and 35 days post-infection (dpi) and processed for histopathological and immunohistochemical analyses. PRRSV antigen was detected in the thymus from 3dpi until the end of the study in all virus-infected animals with the highest numbers of infected cells detected in SU1-bel group. The histomorphometry analysis and counts of CD3+ thymocytes in the thymic cortex displayed significant differences between strains at different time-points (p ≤ 0.011), with SU1-bel group showing the most severe changes at 7dpi. Cell death displayed statistically significant increase in the cortex of all infected animals, with SU1-bel group showing the highest rate at 3 and 7dpi. The number of cells immunostained against IL-1α, TNF-α and IL-10 were predominantly detected in the medulla (p ≤ 0.01). An increase in the number of TNF-α and IL-10 positive cells was observed in LV and SU-1bel groups. Our results demonstrate that different PRRSV-1 strains induced depletion of the thymic cortex due to apoptosis of thymocytes and that the most severe depletion was associated with the highly virulent SU1-bel strain.

  • Dean GS, Clifford D, Whelan AO, Tchilian EZ, Beverley PC, Salguero FJ, Xing Z, Vordermeier HM, Villarreal-Ramos B. (2015) 'Protection Induced by Simultaneous Subcutaneous and Endobronchial Vaccination with BCG/BCG and BCG/Adenovirus Expressing Antigen 85A against Mycobacterium bovis in Cattle.'. PLoS One, United States: 10 (11)
  • Conejero L, Potempa K, Graham CM, Spink N, Blankley S, Salguero FJ, Panka-Sranujit R, Khaenam P, Banchereau JF, Pascual V, Chaussabe D, Lertmemongkochai G, O'Garra A, Bancroft GJ. (2015) 'The Blood Transcriptome of Experimental Melioidosis Reflects Disease Severity and Shows Considerable Similarity with the Human Disease'. AMER ASSOC IMMUNOLOGISTS JOURNAL OF IMMUNOLOGY, 195 (7), pp. 3248-3261.
  • Smither SJ, Nelson M, Eastaugh L, Nunez A, Salguero FJ, Lever MS. (2015) 'Experimental Respiratory Infection of Marmosets (Callithrix jacchus) With Ebola Virus Kikwit'. OXFORD UNIV PRESS INC JOURNAL OF INFECTIOUS DISEASES, 212, pp. S336-S345.
  • Crawshaw TR, Chanter JI, Young SC, Cawthraw S, Whatmore AM, Koylass MS, Vidal AB, Salguero FJ, Irvine RM. (2015) 'Isolation of a novel thermophilic Campylobacter from cases of spotty liver disease in laying hens and experimental reproduction of infection and microscopic pathology.'. Vet Microbiol, Netherlands: 179 (3-4), pp. 315-321.
  • Seifert K, Juhls C, Salguero FJ, Croft SL. (2015) 'Sequential chemoimmunotherapy of experimental visceral leishmaniasis using a single low dose of liposomal amphotericin B and a novel DNA vaccine candidate.'. Antimicrob Agents Chemother, United States: 59 (9), pp. 5819-5823.
  • Risco D, Cuesta JM, Fernández-Llario P, Salguero FJ, Gonçalves P, García-Jiménez WL, Martínez R, Velarde R, de Mendoza MH, Gómez L, de Mendoza JH. (2015) 'Pathological observations of porcine respiratory disease complex (PRDC) in the wild boar (Sus scrofa)'. European Journal of Wildlife Research, 61 (5), pp. 669-679.
  • Salguero FJ, Frossard JP, Rebel JMJ, Stadejek T, Morgan SB, Graham SP, Steinbach F. (2015) 'Host-pathogen interactions during porcine reproductive and respiratory syndrome virus 1 infection of piglets'. Virus Research, 202, pp. 135-143.
  • Amarilla SP, Gómez-Laguna J, Carrasco L, Rodríguez-Gómez IM, Caridad y Ocerín JM, Morgan SB, Graham SP, Frossard JP, Drew TW, Salguero FJ. (2015) 'A comparative study of the local cytokine response in the lungs of pigs experimentally infected with different PRRSV-1 strains: Upregulation of IL-1α in highly pathogenic strain induced lesions'. Veterinary Immunology and Immunopathology, 164 (3-4), pp. 137-147.
  • Riede O, Seifert K, Oswald D, Endmann A, Hock C, Winkler A, Salguero FJ, Schroff M, Croft SL, Juhls C. (2015) 'Preclinical safety and tolerability of a repeatedly administered human leishmaniasis DNA vaccine.'. Gene Ther, England: 22 (8), pp. 628-635.
  • Salguero FJ, Frossard JP, Rebel JM, Stadejek T, Morgan SB, Graham SP, Steinbach F. (2015) 'Host-pathogen interactions during porcine reproductive and respiratory syndrome virus 1 infection of piglets.'. Virus Res, Netherlands: 202, pp. 135-143.
  • García-Nicolás O, Rosales RS, Pallarés FJ, Risco D, Quereda JJ, Graham SP, Frossard JP, Morgan SB, Steinbach F, Drew TW, Strickland TS, Salguero FJ. (2015) 'Comparative analysis of cytokine transcript profiles within mediastinal lymph node compartments of pigs after infection with porcine reproductive and respiratory syndrome genotype 1 strains differing in pathogenicity'. Veterinary Research, 46 (1)
  • Crawshaw TR, Chanter JI, Young SCL, Cawthraw S, Whatmore AM, Koylass MS, Vidal AB, Salguero FJ, Irvine RM. (2015) 'Isolation of a novel thermophilic Campylobacter from cases of spotty liver disease in laying hens and experimental reproduction of infection and microscopic pathology'. Veterinary Microbiology, 179 (3-4), pp. 315-321.
  • Morgan SB, Frossard JP, Pallares FJ, Gough J, Stadejek T, Graham SP, Steinbach F, Drew TW, Salguero FJ. (2014) 'Pathology and Virus Distribution in the Lung and Lymphoid Tissues of Pigs Experimentally Inoculated with Three Distinct Type 1 PRRS Virus Isolates of Varying Pathogenicity.'. Transbound Emerg Dis, Germany: 63 (3), pp. 285-295.
  • Franzoni G, Edwards JC, Kurkure NV, Edgar DS, Sanchez-Cordon PJ, Haines FJ, Salguero FJ, Everett HE, Bodman-Smith KB, Crooke HR, Graham SP. (2014) 'Partial Activation of natural killer and γδ T cells by classical swine fever viruses is associated with type I interferon elicited from plasmacytoid dendritic cells.'. Clin Vaccine Immunol, 21 (10), pp. 1410-1420.
  • Rodríguez-Gómez IM, Barranco I, Amarilla SP, García-Nicolás O, Salguero FJ, Carrasco L, Gómez-Laguna J. (2014) 'Activation of extrinsic- and Daxx-mediated pathways in lymphoid tissue of PRRSV-infected pigs'. Veterinary Microbiology, 172 (1-2), pp. 186-194.
  • García-Nicolás O, Quereda JJ, Gómez-Laguna J, Salguero FJ, Carrasco L, Ramis G, Pallarés FJ. (2014) 'Cytokines transcript levels in lung and lymphoid organs during genotype 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) infection'. Veterinary Immunology and Immunopathology, 160 (1-2), pp. 26-40.
  • Habiela M, Seago J, Perez-Martin E, Waters R, Windsor M, Salguero FJ, Wood J, Charleston B, Juleff N. (2014) 'Laboratory animal models to study foot-and-mouth disease: a review with emphasis on natural and vaccine-induced immunity.'. J Gen Virol, England: 95 (Pt 11), pp. 2329-2345.
  • Dean G, Whelan A, Clifford D, Salguero FJ, Xing Z, Gilbert S, McShane H, Hewinson RG, Vordermeier M, Villarreal-Ramos B. (2014) 'Comparison of the immunogenicity and protection against bovine tuberculosis following immunization by BCG-riming and boosting with adenovirus or protein based vaccines'. Vaccine, 32 (11), pp. 1304-1310.
  • Nelson M, Salguero FJ, Dean RE, Ngugi SA, Smither SJ, Atkins TP, Lever MS. (2014) 'Comparative experimental subcutaneous glanders and melioidosis in the common marmoset (Callithrix jacchus)'. International Journal of Experimental Pathology, 95 (6), pp. 378-391.
  • García-Jiménez WL, Salguero FJ, Fernández-Llario P, Martínez R, Risco D, Gough J, Ortiz-Peláez A, Hermoso-de-Mendoza J, Gómez L. (2013) 'Immunopathology of granulomas produced by Mycobacterium bovis in naturally infected wild boar'. Veterinary Immunology and Immunopathology, 156 (1-2), pp. 54-63.
  • Rodríguez-Gómez IM, Gómez-Laguna J, Barranco I, Pallarés FJ, Ramis G, Salguero FJ, Carrasco L. (2013) 'Downregulation of antigen-presenting cells in tonsil and lymph nodes of porcine reproductive and respiratory syndrome virus-infected pigs'. Transboundary and Emerging Diseases, 60 (5), pp. 425-437.
  • García-Jiménez WL, Fernández-Llario P, Benítez-Medina JM, Cerrato R, Cuesta J, García-Sánchez A, Gonçalves P, Martínez R, Risco D, Salguero FJ, Serrano E, Gómez L, Hermoso-de-Mendoza J. (2013) 'Reducing Eurasian wild boar (Sus scrofa) population density as a measure for bovine tuberculosis control: Effects in wild boar and a sympatric fallow deer (Dama dama) population in Central Spain'. Preventive Veterinary Medicine, 110 (3-4), pp. 435-446.
  • Gómez-Laguna J, Salguero FJ, Fernández de Marco M, Barranco I, Rodríguez-Gómez IM, Quezada M, Carrasco L. (2013) 'Type 2 Porcine Reproductive and Respiratory Syndrome Virus Infection Mediated Apoptosis in B- and T-Cell Areas in Lymphoid Organs of Experimentally Infected Pigs'. Transboundary and Emerging Diseases, 60 (3), pp. 273-278.
  • Jugg B, Fairhall S, Smith A, Rutter S, Mann T, Perrott R, Jenner J, Salguero J, Shute J, Sciuto AM. (2013) 'N-acetyl-L-cysteine protects against inhaled sulfur mustard poisoning in the large swine'. Clinical Toxicology, 51 (4), pp. 216-224.
  • García-Jiménez WL, Benítez-Medina JM, Fernández-Llario P, Abecia JA, García-Sánchez A, Martínez R, Risco D, Ortiz-Peláez A, Salguero FJ, Smith NH, Gómez L, Hermoso de Mendoza J. (2013) 'Comparative Pathology of the Natural infections by Mycobacterium bovis and by Mycobacterium caprae in Wild Boar (Sus scrofa)'. Transboundary and Emerging Diseases, 60 (2), pp. 102-109.
  • Smither SJ, Nelson M, Eastaugh L, Laws TR, Taylor C, Smith SA, Salguero FJ, Lever MS. (2013) 'Experimental respiratory Marburg virus haemorrhagic fever infection in the common marmoset (Callithrix jacchus)'. International Journal of Experimental Pathology, 94 (2), pp. 156-168.
  • Gómez-Laguna J, Salguero FJ, Pallarés FJ, Carrasco L. (2013) 'Immunopathogenesis of porcine reproductive and respiratory syndrome in the respiratory tract of pigs'. Veterinary Journal, 195 (2), pp. 148-155.
  • Konold T, Moore SJ, Bellworthy SJ, Terry LA, Thorne L, Ramsay A, Salguero FJ, Simmons MM, Simmons HA. (2013) 'Evidence of effective scrapie transmission via colostrum and milk in sheep'. BIOMED CENTRAL LTD BMC VETERINARY RESEARCH, 9 Article number ARTN 99
  • Laws TR, Nelson M, Bonnafous C, Sicard H, Taylor C, Salguero FJ, Atkins TP, Oyston PCF, Rowland CA. (2013) 'In Vivo Manipulation of gamma 9(+) T Cells in the Common Marmoset (Callithrix Jacchus) with Phosphoantigen and Effect on the Progression of Respiratory Melioidosis'. PUBLIC LIBRARY SCIENCE PLOS ONE, 8 (9) Article number ARTN e74789
  • Morgan SB, Graham SP, Sánchez Cordón PJ, Mokhtar H, Steinbach F, Frossard JP, Bodman-Smith KB, Salguero FJ, Rebel JMJ, Weesendorp E. (2013) 'Increased pathogenicity of European porcine reproductive and respiratory syndrome virus is associated with enhanced adaptive responses and viral clearance'. Veterinary Microbiology,
  • Barranco I, Gómez-Laguna J, Rodríguez-Gómez IM, Quereda JJ, Salguero FJ, Pallarés FJ, Carrasco L. (2012) 'Immunohistochemical expression of IL-12, IL-10, IFN-α and IFN-γ in lymphoid organs of porcine reproductive and respiratory syndrome virus-infected pigs'. Veterinary Immunology and Immunopathology, 149 (3-4), pp. 262-271.
  • García-Jiménez WL, Fernández-Llario P, Gómez L, Benítez-Medina JM, García-Sánchez A, Martínez R, Risco D, Gough J, Ortiz-Peláez A, Smith NH, Mendoza JHD, Salguero FJ. (2012) 'Histological and immunohistochemical characterisation of Mycobacterium bovis induced granulomas in naturally infected Fallow deer (Dama dama)'. Veterinary Immunology and Immunopathology, 149 (1-2), pp. 66-75.
  • Aranday-Cortes E, Bull NC, Villarreal-Ramos B, Gough J, Hicks D, Ortiz-Peláez A, Vordermeier HM, Salguero FJ. (2012) 'Upregulation of IL-17A, CXCL9 and CXCL10 in Early-Stage Granulomas Induced by Mycobacterium bovis in Cattle'. Transboundary and Emerging Diseases, 60 (6), pp. 525-537.
  • Gómez-Laguna J, Rodríguez-Gómez IM, Barranco I, Pallarés FJ, Salguero FJ, Carrasco L. (2012) 'Enhanced expression of TGFβ protein in lymphoid organs and lung, but not in serum, of pigs infected with a European field isolate of porcine reproductive and respiratory syndrome virus'. Veterinary Microbiology, 158 (1-2), pp. 187-193.
  • Barranco I, Gómez-Laguna J, Rodríguez-Gómez IM, Salguero FJ, Pallarés FJ, Carrasco L. (2012) 'Differential Expression of Proinflammatory Cytokines in the Lymphoid Organs of Porcine Reproductive and Respiratory Syndrome Virus-Infected Pigs'. Transboundary and Emerging Diseases, 59 (2), pp. 145-153.
  • Graham SP, Everett HE, Haines FJ, Johns HL, Sosan OA, Salguero FJ, Clifford DJ, Steinbach F, Drew TW, Crooke HR. (2012) 'Challenge of Pigs with Classical Swine Fever Viruses after C-Strain Vaccination Reveals Remarkably Rapid Protection and Insights into Early Immunity'. PUBLIC LIBRARY SCIENCE PLOS ONE, 7 (1) Article number ARTN e29310
  • Lever MS, Piercy TJ, Steward JA, Eastaugh L, Smither SJ, Taylor C, Salguero FJ, Phillpotts RJ. (2012) 'Lethality and pathogenesis of airborne infection with filoviruses in A129 α/β -/- interferon receptor-deficient mice'. Journal of Medical Microbiology, 61 (1), pp. 8-15.
  • Nelson M, Dean RE, Salguero FJ, Taylor C, Pearce PC, Simpson AJH, Lever MS. (2011) 'Development of an acute model of inhalational melioidosis in the common marmoset (Callithrix jacchus)'. WILEY-BLACKWELL INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 92 (6), pp. 428-435.
  • Argilaguet JM, Pérez-Martín E, Gallardo C, Salguero FJ, Borrego B, Lacasta A, Accensi F, Díaz I, Nofrarías M, Pujols J, Blanco E, Pérez-Filgueira M, Escribano JM, Rodríguez F. (2011) 'Enhancing dna immunization by targeting asfv antigens to sla-ii bearing cells'. Vaccine, 29 (33), pp. 5379-5385.
  • Conejero L, Patel N, De Reynal M, Oberdorf S, Prior J, Felgner PL, Titball RW, Salguero FJ, Bancroft GJ. (2011) 'Low-dose exposure of C57BL/6 mice to Burkholderia pseudomallei mimics chronic human melioidosis'. American Journal of Pathology, 179 (1), pp. 270-280.
  • Lesellier S, Palmer S, Gowtage-Sequiera S, Ashford R, Dalley D, Davé D, Weyer U, Salguero FJ, Nunez A, Crawshaw T, Corner LAL, Hewinson RG, Chambers MA. (2011) 'Protection of Eurasian badgers (Meles meles) from tuberculosis after intra-muscular vaccination with different doses of BCG'. Vaccine, 29 (21), pp. 3782-3790.
  • Senior NJ, Bagnall MC, Champion OL, Reynolds SE, La Ragione RM, Woodward MJ, Salguero FJ, Titball RW. (2011) 'Galleria mellonella as an infection model for Campylobacter jejuni virulence.'. J Med Microbiol, England: 60 (Pt 5), pp. 661-669.
  • Barranco I, Gómez-Laguna J, Rodríguez-Gómez IM, Salguero FJ, Pallarés FJ, Bernabé A, Carrasco L. (2011) 'Immunohistochemical detection of extrinsic and intrinsic mediators of apoptosis in porcine paraffin-embedded tissues'. Veterinary Immunology and Immunopathology, 139 (2-4), pp. 210-216.
  • Gómez-Laguna J, Salguero FJ, Pallarés FJ, Fernández de Marco M, Barranco I, Cerón JJ, Martínez-Subiela S, Van Reeth K, Carrasco L. (2010) 'Acute phase response in porcine reproductive and respiratory syndrome virus infection'. Comparative Immunology, Microbiology and Infectious Diseases, 33 (6)
  • Salguero FJ, Lesellier S, Nunez A, Corner L, Crawshaw T, Chambers M. (2010) 'INTRAMUSCULAR BCG VACCINATION REDUCES SIGNIFICANTLY THE PATHOLOGY INDUCED BY MYCOBACTERIUM BOVIS IN BADGERS (MELES MELES)'. ELSEVIER SCI LTD JOURNAL OF COMPARATIVE PATHOLOGY, 143 (4), pp. 347-347.
  • Barranco I, Gomez-Laguna J, Rodriguez-Gomez IR, Salguero FJ, Pallares FJ, Carrasco L, Bernabe A. (2010) 'ROLE OF CYTOKINES AS MEDIATORS OF THE LOCAL IMMUNE RESPONSE IN LUNG AND TONSIL OF PIGS INOCULATED WITH A EUROPEAN PRRSV FIELD ISOLATE'. ELSEVIER SCI LTD JOURNAL OF COMPARATIVE PATHOLOGY, 143 (4), pp. 321-321.
  • Nelson M, Lever MS, Dean RE, Savage VL, Salguero FJ, Pearce PC, Stevens DJ, Simpson AJH. (2010) 'Characterization of lethal inhalational infection with Francisella tularensis in the common marmoset (Callithrix jacchus)'. SOC GENERAL MICROBIOLOGY JOURNAL OF MEDICAL MICROBIOLOGY, 59 (9), pp. 1107-1113.
  • Srivastava AK, Meenowa D, Barden G, Salguero FJ, Churchward C, Nicholas RAJ. (2010) 'Contagious caprine pleuropneumonia in Mauritius'. Veterinary Record, 167 (8), pp. 304-305.
  • Collins JW, Coldham NG, Salguero FJ, Cooley WA, Newell WR, Rastall RA, Gibson GR, Woodward MJ, La Ragione RM. (2010) 'Response of porcine intestinal In Vitro organ culture tissues following exposure to Lactobacillus plantarum JC1 and Salmonella enterica serovar typhimurium SL1344'. Applied and Environmental Microbiology, 76 (19), pp. 6645-6657.
  • Gómez-Laguna J, Gutiérrez A, Pallarés FJ, Salguero FJ, Cerón JJ, Carrasco L. (2010) 'Haptoglobin and C-reactive protein as biomarkers in the serum, saliva and meat juice of pigs experimentally infected with porcine reproductive and respiratory syndrome virus'. Veterinary Journal, 185 (1), pp. 83-87.
  • Everett H, Salguero FJ, Graham SP, Haines F, Johns H, Clifford D, Nunez A, La Rocca SA, Parchariyanon S, Steinbach F, Drew T, Crooke H. (2010) 'Characterisation of experimental infections of domestic pigs with genotype 2.1 and 3.3 isolates of classical swine fever virus'. Veterinary Microbiology, 142 (1-2), pp. 26-33.
  • Salguero FJ, Richard A, Gough J, Long A, Weyer U, Cooley WA, Chambers MA, Lesellier S. (2010) 'Pelioid Hepatocellular Carcinoma in an Adult Eurasian Badger (Meles meles)'. ELSEVIER SCI LTD JOURNAL OF COMPARATIVE PATHOLOGY, 142 (2-3), pp. 208-212.
  • Gómez-Laguna J, Salguero FJ, Barranco I, Pallarés FJ, Rodríguez-Gómez IM, Bernabé A, Carrasco L. (2010) 'Cytokine Expression by Macrophages in the Lung of Pigs Infected with the Porcine Reproductive and Respiratory Syndrome Virus'. Journal of Comparative Pathology, 142 (1), pp. 51-60.
  • Rodriguez-Gomez IM, Gomez-Laguna J, Barranco I, Salguero FJ, Pallares FJ, Bernabe A, Carrasco L. (2009) 'PROINFLAMMATORY CYTOKINE EXPRESSION IN PRRSV INFECTION: PARACRINE SYNTHESIS AND CORRELATION WITH THE EXTENT OF LUNG LESIONS'. ELSEVIER SCI LTD JOURNAL OF COMPARATIVE PATHOLOGY, 141 (4), pp. 271-271.
  • Gomez-Laguna J, Barranco I, Rodriguez-Gomez IM, Salguero FJ, Pallares FJ, Ahumada P, Carrasco L. (2009) 'MODULATION OF THE PULMONARY IMMUNE RESPONSE BY CYTOKINE EXPRESSION IN PRRS'. ELSEVIER SCI LTD JOURNAL OF COMPARATIVE PATHOLOGY, 141 (4), pp. 271-271.
  • Barranco I, Gomez-Laguna J, Rodriguez-Gomez IM, Salguero FJ, Pallares FJ, Bernabe A, Carrasco L. (2009) 'EVALUATION OF APOPTOSIS AND EXPRESSION OF PROINFLAMMATORY CYTOKINES IN THE TONSIL OF PIGS INFECTED WITH A EUROPEAN PRRSV FIELD ISOLATE'. ELSEVIER SCI LTD JOURNAL OF COMPARATIVE PATHOLOGY, 141 (4), pp. 271-271.
  • Gómez-Laguna J, Salguero FJ, De Marco MF, Pallarés FJ, Bernabé A, Carrasco L. (2009) 'Changes in lymphocyte subsets and cytokines during European porcine reproductive and respiratory syndrome: Increased expression of IL-12 and IL-10 and proliferation of CD4-CD8high'. Viral Immunology, 22 (4), pp. 261-271.
  • Nelson M, Lever MS, Savage VL, Salguero FJ, Pearce PC, Stevens DJ, Simpson AJH. (2009) 'Establishment of lethal inhalational infection with Francisella tularensis (tularaemia) in the common marmoset (Callithrix jacchus)'. WILEY-BLACKWELL PUBLISHING, INC INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 90 (2), pp. 109-118.
  • Alejo A, Saraiva M, Ruiz-Argüello MB, Viejo-Borbolla A, de Marco MF, Salguero FJ, Alcami A. (2009) 'A method for the generation of ectromelia virus (ECTV) recombinants: in vivo analysis of ECTV vCD30 deletion mutants.'. PLoS One, United States: 4 (4)
  • Searle LE, Best A, Nunez A, Salguero FJ, Johnson L, Weyer U, Dugdale AH, Cooley WA, Carter B, Jones G, Tzortzis G, Woodward MJ, La Ragione RM. (2009) 'A mixture containing galactooligosaccharide, produced by the enzymic activity of Bifidobacterium bifidum, reduces Salmonella enterica serovar Typhimurium infection in mice.'. J Med Microbiol, England: 58 (Pt 1), pp. 37-48.
  • Domínguez-Bernal G, Tierrez A, Bartolomé A, Martínez-Pulgarín S, Salguero FJ, Antonio Orden J, de la Fuente R. (2008) 'Salmonella enterica serovar Choleraesuis derivatives harbouring deletions in rpoS and phoP regulatory genes are attenuated in pigs, and survive and multiply in porcine intestinal macrophages and fibroblasts, respectively.'. Vet Microbiol, Netherlands: 130 (3-4), pp. 298-311.
  • Salguero FJ, Gil S, Revilla Y, Gallardo C, Arias M, Martins C. (2008) 'Cytokine mRNA expression and pathological findings in pigs inoculated with African swine fever virus (E-70) deleted on A238L.'. Vet Immunol Immunopathol, Netherlands: 124 (1-2), pp. 107-119.
  • Fernández de Marco M, Salguero FJ, Bautista MJ, Núñez A, Sánchez-Cordón PJ, Gómez-Villamandos JC. (2007) 'An immunohistochemical study of the tonsils in pigs with acute African swine fever virus infection.'. Res Vet Sci, England: 83 (2), pp. 198-203.
  • Espinosa JC, Andréoletti O, Castilla J, Herva ME, Morales M, Alamillo E, San-Segundo FD, Lacroux C, Lugan S, Salguero FJ, Langeveld J, Torres JM. (2007) 'Sheep-passaged bovine spongiform encephalopathy agent exhibits altered pathobiological properties in bovine-PrP transgenic mice.'. J Virol, United States: 81 (2), pp. 835-843.
  • Díaz-San Segundo F, Salguero FJ, de Avila A, Espinosa JC, Torres JM, Brun A. (2006) 'Distribution of the cellular prion protein (PrPC) in brains of livestock and domesticated species.'. Acta Neuropathol, Germany: 112 (5), pp. 587-595.
  • Fernandez-Borges N, Brun A, Whitton JL, Parra B, Diaz-San Segundo F, Salguero FJ, Torres JM, Rodriguez F. (2006) 'DNA vaccination can break immunological tolerance to PrP in wild-type mice and attenuates prion disease after intracerebral challenge.'. J Virol, United States: 80 (20), pp. 9970-9976.
  • Bautista MJ, Gutiérrez J, Salguero FJ, Fernández de Marco MM, Romero-Trevejo JL, Gómez-Villamandos JC. (2006) 'BSE infection in bovine PrP transgenic mice leads to hyperphosphorylation of tau-protein.'. Vet Microbiol, Netherlands: 115 (4), pp. 293-301.
  • Jimenez N, Coll J, Salguero FJ, Tafalla C. (2006) 'Co-injection of interleukin 8 with the glycoprotein gene from viral haemorrhagic septicemia virus (VHSV) modulates the cytokine response in rainbow trout (Oncorhynchus mykiss).'. Vaccine, Netherlands: 24 (27-28), pp. 5615-5626.
  • Gómez-Villamandos JC, García de Leániz I, Núñez A, Salguero FJ, Ruiz-Villamor E, Romero-Trevejo JL, Sánchez-Cordón PJ. (2006) 'Neuropathologic study of experimental classical swine fever.'. Vet Pathol, United States: 43 (4), pp. 530-540.
  • Díaz-San Segundo F, Salguero FJ, de Avila A, de Marco MM, Sánchez-Martín MA, Sevilla N. (2006) 'Selective lymphocyte depletion during the early stage of the immune response to foot-and-mouth disease virus infection in swine.'. J Virol, United States: 80 (5), pp. 2369-2379.
  • Salguero FJ, Díaz-San SF, Brun A, Cano MJ, Torres JM. (2006) 'Comparison of three monoclonal antibodies for use in immunohistochemical detection of bovine spongiform encephalopathy protease-resistant prion protein.'. J Vet Diagn Invest, United States: 18 (1), pp. 106-109.
  • Castilla J, Gutiérrez-Adán A, Brun A, Pintado B, Salguero FJ, Parra B, Segundo FD, Ramírez MA, Rábano A, Cano MJ, Torres JM. (2005) 'Transgenic mice expressing bovine PrP with a four extra repeat octapeptide insert mutation show a spontaneous, non-transmissible, neurodegenerative disease and an expedited course of BSE infection.'. FEBS Lett, Netherlands: 579 (27), pp. 6237-6246.
  • Sánchez-Cordón PJ, Núñez A, Salguero FJ, Pedrera M, Fernández de Marco M, Gómez-Villamandos JC. (2005) 'Lymphocyte apoptosis and thrombocytopenia in spleen during classical swine fever: role of macrophages and cytokines.'. Vet Pathol, United States: 42 (4), pp. 477-488.
  • Castilla J, Brun A, Díaz-San Segundo F, Salguero FJ, Gutiérrez-Adán A, Pintado B, Ramírez MA, del Riego L, Torres JM. (2005) 'Vertical transmission of bovine spongiform encephalopathy prions evaluated in a transgenic mouse model.'. J Virol, United States: 79 (13), pp. 8665-8668.
  • Núñez A, Gómez-Villamandos JC, Sánchez-Cordón PJ, Fernández de Marco M, Pedrera M, Salguero FJ, Carrasco L. (2005) 'Expression of proinflammatory cytokines by hepatic macrophages in acute classical swine fever.'. J Comp Pathol, England: 133 (1), pp. 23-32.
  • Sánchez-Cordón PJ, Núñez A, Salguero FJ, Carrasco L, Gómez-Villamandos JC. (2005) 'Evolution of T lymphocytes and cytokine expression in classical swine fever (CSF) virus infection.'. J Comp Pathol, England: 132 (4), pp. 249-260.
  • Salguero FJ, Sánchez-Cordón PJ, Núñez A, Fernández de Marco M, Gómez-Villamandos JC. (2005) 'Proinflammatory cytokines induce lymphocyte apoptosis in acute African swine fever infection.'. J Comp Pathol, England: 132 (4), pp. 289-302.
  • Salguero FJ, Sánchez-Martín MA, Díaz-San Segundo F, de Avila A, Sevilla N. (2005) 'Foot-and-mouth disease virus (FMDV) causes an acute disease that can be lethal for adult laboratory mice.'. Virology, United States: 332 (1), pp. 384-396.
  • Carrasco L, Núñez A, Sánchez-Cordón PJ, Pedrera M, Fernández de Marco M, Salguero FJ, Gómez-Villamandos JC. (2004) 'Immunohistochemical detection of the expression of pro-inflammatory cytokines by ovine pulmonary macrophages.'. J Comp Pathol, England: 131 (4), pp. 285-293.
  • Castilla J, Gutiérrez-Adán A, Brun A, Doyle D, Pintado B, Ramírez MA, Salguero FJ, Parra B, Segundo FD, Sánchez-Vizcaíno JM, Rogers M, Torres JM. (2004) 'Subclinical bovine spongiform encephalopathy infection in transgenic mice expressing porcine prion protein.'. J Neurosci, United States: 24 (21), pp. 5063-5069.
  • Castilla J, Gutiérrez-Adán A, Brun A, Pintado B, Parra B, Ramírez MA, Salguero FJ, Díaz San Segundo F, Rábano A, Cano MJ, Torres JM. (2004) 'Different behavior toward bovine spongiform encephalopathy infection of bovine prion protein transgenic mice with one extra repeat octapeptide insert mutation.'. J Neurosci, United States: 24 (9), pp. 2156-2164.
  • Salguero FJ, Sánchez-Cordón PJ, Sierra MA, Jover A, Núñez A, Gómez-Villamandos JC. (2004) 'Apoptosis of thymocytes in experimental African Swine Fever virus infection.'. Histol Histopathol, Spain: 19 (1), pp. 77-84.
  • Brun A, Castilla J, Ramírez MA, Prager K, Parra B, Salguero FJ, Shiveral D, Sánchez C, Sánchez-Vizcaíno JM, Douglas A, Torres JM. (2004) 'Proteinase K enhanced immunoreactivity of the prion protein-specific monoclonal antibody 2A11.'. Neurosci Res, Ireland: 48 (1), pp. 75-83.
  • Sánchez-Cordón PJ, Romanini S, Salguero FJ, Ruiz-Villamor E, Carrasco L, Gómez-Villamandos JC. (2003) 'A histopathologic, immunohistochemical, and ultrastructural study of the intestine in pigs inoculated with classical swine fever virus.'. Vet Pathol, United States: 40 (3), pp. 254-262.
  • Gómez-Villamandos JC, Carrasco L, Bautista MJ, Sierra MA, Quezada M, Hervas J, Chacón MDEL, Ruiz-Villamor E, Salguero FJ, Sónchez-Cordón PJ, Romanini S, Núñez A, Mekonen T, Méndez A, Jover A. (2003) 'African swine fever and classical swine fever: a review of the pathogenesis.'. Dtsch Tierarztl Wochenschr, Germany: 110 (4), pp. 165-169.
  • Castilla J, Gutiérrez Adán A, Brun A, Pintado B, Ramírez MA, Parra B, Doyle D, Rogers M, Salguero FJ, Sánchez C, Sánchez-Vizcaíno JM, Torres JM. (2003) 'Early detection of PrPres in BSE-infected bovine PrP transgenic mice.'. Arch Virol, Austria: 148 (4), pp. 677-691.
  • Gomez-Villamandos JC, Salguero FJ, Ruiz-Villamor E, Sánchez-Cordón PJ, Bautista MJ, Sierra MA. (2003) 'Classical Swine Fever: pathology of bone marrow.'. Vet Pathol, United States: 40 (2), pp. 157-163.
  • Carrasco L, Madsen LW, Salguero FJ, Núñez A, Sánchez-Cordón P, Bollen P. (2003) 'Immune complex-associated thrombocytopenic purpura syndrome in sexually mature Göttingen minipigs.'. J Comp Pathol, England: 128 (1), pp. 25-32.
  • Sánchez-Cordón PJ, Romanini S, Salguero FJ, Núñez A, Bautista MJ, Jover A, Gómez-Villamos JC. (2002) 'Apoptosis of thymocytes related to cytokine expression in experimental classical swine fever.'. J Comp Pathol, England: 127 (4), pp. 239-248.
  • Salguero FJ, Ruiz-Villamor E, Bautista MJ, Sánchez-Cordón PJ, Carrasco L, Gómez-Villamandos JC. (2002) 'Changes in macrophages in spleen and lymph nodes during acute African swine fever: expression of cytokines.'. Vet Immunol Immunopathol, Netherlands: 90 (1-2), pp. 11-22.
  • Sánchez-Cordón PJ, Salguero FJ, Núnez A, Gómez-Villamandos JC, Carrasco L. (2002) 'Glomerulonephritis associated with simultaneous canine adenovirus-1 and Dirofilaria immitis infection in a dog.'. J Vet Med B Infect Dis Vet Public Health, Germany: 49 (5), pp. 235-239.
  • Sánchez-Cordón PJ, Hervás J, Chacón de Lara F, Jahn J, Salguero FJ, Gómez-Villamandos JC. (2002) 'Reovirus infection in psittacine birds (Psittacus erithacus): morphologic and immunohistochemical study.'. Avian Dis, United States: 46 (2), pp. 485-492.
  • Salguero FJ, Sánchez-Cordón PJ, Núñez A, Gómez-Villamandos JC. (2002) 'Histopathological and ultrastructural changes associated with herpesvirus infection in waterfowl.'. Avian Pathol, England: 31 (2), pp. 133-140.
  • Carrasco L, Núñez A, Salguero FJ, Díaz San Segundo F, Sánchez-Cordón P, Gómez-Villamandos JC, Sierra MA. (2002) 'African swine fever: Expression of interleukin-1 alpha and tumour necrosis factor-alpha by pulmonary intravascular macrophages.'. J Comp Pathol, England: 126 (2-3), pp. 194-201.
  • Bautista MJ, Ruiz-Villamor E, Salguero FJ, Sánchez-Cordón PJ, Carrasco L, Gómez-Villamandos JC. (2002) 'Early platelet aggregation as a cause of thrombocytopenia in classical swine fever.'. Vet Pathol, United States: 39 (1), pp. 84-91.
  • Salguero FJ, Mekonnen T, Ruiz-Villamor E, Sánchez-Cordón PJ, Gómez-Villamandos JC. (2001) 'Detection of monokines in paraffin-embedded tissues of pigs using polyclonal antibodies.'. Vet Res, France: 32 (6), pp. 601-609.
  • Carrasco L, Lima JS, Halfen DC, Salguero FJ, Sánchez-Cordon P, Becker G. (2001) 'Systemic aspergillosis in an oiled magallanic penguin (Spheniscus magellanicus).'. J Vet Med B Infect Dis Vet Public Health, Germany: 48 (7), pp. 551-554.
  • Gómez-Villamandos JC, Ruiz-Villamor E, Bautista MJ, Sánchez CP, Sánchez-Cordón PJ, Salguero FJ, Jover A. (2001) 'Morphological and immunohistochemical changes in splenic macrophages of pigs infected with classical swine fever.'. J Comp Pathol, England: 125 (2-3), pp. 98-109.
  • Carrasco L, Ruiz-Villamor E, Gómez-Villamandos JC, Salguero FJ, Bautista MJ, Maciá M, Quezada M, Jover A. (2001) 'Classical swine fever: morphological and morphometrical study of pulmonary intravascular macrophages.'. J Comp Pathol, England: 125 (1), pp. 1-7.
  • Ruiz-Villamor E, Quezada M, Bautista MJ, Romanini S, Carrasco L, Salguero FJ, Gómez-Villamandos JC. (2001) 'Classical swine fever: pathogenesis of glomerular damage and immunocharacterization of immunocomplex deposits.'. J Comp Pathol, England: 124 (4), pp. 246-254.
  • Gómez-Villamandos JC, Ruiz-Villamor E, Bautista MJ, Quezada M, Sánchez CP, Salguero FJ, Sierra MA. (2000) 'Pathogenesis of classical swine fever: renal haemorrhages and erythrodiapedesis.'. J Comp Pathol, ENGLAND: 123 (1), pp. 47-54.
  • Scarlata E, Salguero JJ, Hervás J, Chacon F, De Lara M, Jahn J, Gómez-Villamandos JC. (1999) 'Filamentous intranuclear inclusion bodies in psittacine birds. A structural and ultrastructural study'. Journal of Veterinary Medicine, Series B, 46 (6), pp. 375-380.
  • Gómez-Villamandos JC, Ruiz-Villamor E, Salguero FJ, Bautista MJ, Carrasco L, Sánchez C, Quezada M, Sierra MA. (1998) 'Immunohistochemical and ultrastructural evidence of hog cholera virus infection of megakaryocytes in bone marrow and spleen.'. J Comp Pathol, ENGLAND: 119 (2), pp. 111-119.
  • Bautista MJ, Gómez-Villamandos JC, Carrasco L, Ruíz-Villamor E, Salguero FJ, Sierra MA. (1998) 'Ultrastructural pathology of the bone marrow in pigs inoculated with a moderately virulent strain (DR'78) of African swine fever virus.'. Histol Histopathol, SPAIN: 13 (3), pp. 713-720.
  • Gomex-Villamandos JC, Hervas J, Salguero FJ, Quevedo MA, Aguilar JM, Mozos E. (1998) 'Haemorrhagic enteritis associated with herpesvirus in storks.'. Avian Pathol, England: 27 (3), pp. 229-236.

Conference papers

  • Morgan SB, Graham SP, Salguero J, Steinbach F, Frossard JP. (2012) 'Increased pathology during infection with an atypical European porcine Arterivirus correlates with an enhanced adaptive immune response'. WILEY-BLACKWELL IMMUNOLOGY, Glasgow, SCOTLAND: European Congress of Immunology 137, pp. 641-641.

Theses and dissertations

  • Ashpitel H. (2018) The effects of endothermal ablation devices on the vein wall : a histological and immunohistochemical examination..
    [ Status: Approved ]

    Abstract

    Varicose veins, often thought as a purely cosmetic issue, are a common symptom resulting from chronic venous insufficiency (CVI). CVI can result in serious fasciocutaneous and haematological complications. In 2013, NICE recommended that the treatment of varicose veins should preferably be carried out by endothermal ablation (ETA). The mechanism of action of ETA is still not fully understood. In 2004 it was suggested that successful treatment must involve transmural vein wall death (TMVD) in the target vein. Through the development of a novel in-vitro¬ model, using ex-vivo veins, the work carried out in this thesis has indicated that TMVD is reliant on a combination of thermal necrosis, followed by the upregulation of apoptosis. The novel model has been used to compare four different ETA techniques; endovenous laser ablation (EVLA) using an 810nm endovenous laser (EVL) with a jacketed fibre, EVLA using a 1470nm EVL with a jacketed fibre, EVLA using a 1470nm EVL with a radial fibre and Radiofrequency-induced Thermo Therapy (RFiTT). The comparisons indicate that treatment with the 810nm EVL is inferior at causing TMVD, in comparison to the 1470nm EVL. Treatment with a radial fibre, compared to a jacketed fibre, when using a 1470nm EVL, shows an improved damage profile that is much more homogenous with less overtreatment of target tissue. Comparisons between RFiTT and EVLA, indicate that treatment with RFiTT is as effective at causing TMVD as the 1470nm EVL with a radial fibre but with differences in the thermal damage profile. These results correlate well with reports from the current literature. However, this novel model has been able to show that the upregulation of apoptosis plays a pivotal role in TMVD after ETA treatment. The results also show that histology is often not sufficient to alone determine the difference between successful and inadequate treatment.

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