Kikki Bodman-Smith

Dr Kikki Bodman-Smith


School Director for Learning and Teaching, Lecturer in Immunology, Director of Biomedical Science Programmes
BSc, PhD
+44 (0)1483 689736
31 AX 01
Monday - Friday

Biography

Biography

  • BSc Biology, Royal Holloway and Bedford New College, University of London
  • PhD Immunology, University College London, University of London
  • Postdoctoral Research Fellow: Department of Surgery, University College London, University of London
  • Immunology Group, London School of Hygiene and Tropical Medicine, University of London
  • Lecturer in Immunolgy, Faculty of Health and Medical Sciences, University of Surrey

Research Interests

Current research interests lie in understanding the role of the inflammatory acute phase proteins in innate immune responses to infection and in inflammatory disease and how they may interact with the acquired immune response. This can be further divided into (i) The effect of acute phase proteins on host cells particularly in relation to inflammatory disease (ii) Host cell receptors used by acute phase proteins for pathogen uptake and (iii) The role of acute phase proteins on pathogen survival.

Research Collaborations

Dr Graham Stewart

Professor Johnjoe McFadden

Ernesto Oviedo-Orta and the Cardiovascular research group

My publications

Publications

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 ³´ 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
Vaccination with live attenuated classical swine fever virus (CSFV) vaccines can rapidly confer protection in the absence of neutralizing antibodies. With an aim of providing information on the cellular mechanisms that may mediate this protection, we explored the interaction of porcine natural killer (NK) cells and ³´ T cells with CSFV. Both NK and ³´ T cells were refractory to infection with attenuated or virulent CSFV, and no stimulatory effects, as assessed by the expression of major histocompatibility complex (MHC) class II (MHC-II), perforin, and gamma interferon (IFN-³), were observed when the cells were cultured in the presence of CSFV. Coculture with CSFV and myeloid dendritic cells (mDCs) or plasmacytoid dendritic cells (pDCs) showed that pDCs led to a partial activation of both NK and ³´ T cells, with upregulation of MHC-II being observed. An analysis of cytokine expression by infected DC subsets suggested that this effect was due to IFN-± secreted by infected pDCs. These results were supported by ex vivo analyses of NK and ³´ T cells in the tonsils and retropharyngeal lymph nodes from pigs that had been vaccinated with live attenuated CSFV and/or virulent CSFV. At 5 days postchallenge, there was evidence of significant upregulation of MHC-II but not perforin on NK and ³´ T cells, which was observed only following a challenge of the unvaccinated pigs and correlated with increased CSFV replication and IFN-± expression in both the tonsils and serum. Together, these data suggest that it is unlikely that NK or ³´ T cells contribute to the cellular effector mechanisms induced by live attenuated CSFV.
Karam MC, Hamdan HG, Abi Chedid NA, Baroody GM, Bodman-Smith KB (2007) Interleukin-10 reduces hyperalgesia and the level of Interleukin-1² in BALB/c mice infected with Leishmania major with no major effect on the level of Interleukin-6, Journal of Neuroimmunology 183 (1-2) pp. 43-49
Infection with a high dose of Leishmania major has been shown to induce hyperalgesia in BALB/c mice accompanied by a sustained upregulation of Interleukin-1² (IL-1²) and an early upregulation of Interleukin-6 (IL-6). On the other hand, Interleukin 10 (IL-10) has been demonstrated to be hypoalgesic in other models such as rats exposed to UV rays. In this study, we injected BALB/c mice with a high dose of Leishmania major and treated them with IL-10 (15 ng/animal) for six consecutive days. Hyperalgesia was assessed using thermal pain tests and the levels of IL-1² and IL-6 were also assessed at different post-infection days. Our results show that IL-10 can reduce the Leishmania major-induced hyperalgesia during the treatment period through a direct effect on the levels of IL-1² which seems to play an important role in this hyperalgesia induction since its level was reduced during the period of IL-10 injection and was increased again when this treatment was stopped. On the contrary IL-10 has no direct effect on the levels IL-6 which seems to have no direct role in the induced hyperalgesia. © 2006 Elsevier B.V. All rights reserved.
Rayman MP, Searle E, Kelly L, Johnsen S, Bodman-Smith K, Bath SC, Mao J, Redman CWG (2014) Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: A randomised, controlled pilot trial, British Journal of Nutrition 112 (1) pp. 99-111
Pre-eclampsia is a serious hypertensive condition of pregnancy associated with high maternal and fetal morbidity and mortality. Se intake or status has been linked to the occurrence of pre-eclampsia by our own work and that of others. We hypothesised that a small increase in the Se intake of UK pregnant women of inadequate Se status would protect against the risk of pre-eclampsia, as assessed by biomarkers of pre-eclampsia. In a double-blind, placebo-controlled, pilot trial, we randomised 230 primiparous pregnant women to Se (60 ¼g/d, as Se-enriched yeast) or placebo treatment from 12 to 14 weeks of gestation until delivery. Whole-blood Se concentration was measured at baseline and 35 weeks, and plasma selenoprotein P (SEPP1) concentration at 35 weeks. The primary outcome measure of the present study was serum soluble vascular endothelial growth factor receptor-1 (sFlt-1), an anti-angiogenic factor linked with the risk of pre-eclampsia. Other serum/plasma components related to the risk of pre-eclampsia were also measured. Between 12 and 35 weeks, whole-blood Se concentration increased significantly in the Se-treated group but decreased significantly in the placebo group. At 35 weeks, significantly higher concentrations of whole-blood Se and plasma SEPP1 were observed in the Se-treated group than in the placebo group. In line with our hypothesis, the concentration of sFlt-1 was significantly lower at 35 weeks in the Se-treated group than in the placebo group in participants in the lowest quartile of Se status at baseline (P=0·039). None of the secondary outcome measures was significantly affected by treatment. The present finding that Se supplementation has the potential to reduce the risk of pre-eclampsia in pregnant women of low Se status needs to be validated in an adequately powered trial. Copyright © The Author(s) [2014] The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution licence.
Rodriguez JA, Bodman-Smith KB, Raynes JG (2004) Neutrophil responses to C-reactive protein are not dependent on polymorphism R/H131 of human Fc³RIIa, Clinical and Experimental Immunology 138 (2) pp. 271-277 Blackwell Publishing Limited
Rayman MP, Searle E, Kelly L, Johnsen S, Bodman-Smith K, Bath SC, Mao J, Redman CW (2014) Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: a randomised, controlled pilot trial., Br J Nutr 112 (1) pp. 99-111
Pre-eclampsia is a serious hypertensive condition of pregnancy associated with high maternal and fetal morbidity and mortality. Se intake or status has been linked to the occurrence of pre-eclampsia by our own work and that of others. We hypothesised that a small increase in the Se intake of UK pregnant women of inadequate Se status would protect against the risk of pre-eclampsia, as assessed by biomarkers of pre-eclampsia. In a double-blind, placebo-controlled, pilot trial, we randomised 230 primiparous pregnant women to Se (60 ¼g/d, as Se-enriched yeast) or placebo treatment from 12 to 14 weeks of gestation until delivery. Whole-blood Se concentration was measured at baseline and 35 weeks, and plasma selenoprotein P (SEPP1) concentration at 35 weeks. The primary outcome measure of the present study was serum soluble vascular endothelial growth factor receptor-1 (sFlt-1), an anti-angiogenic factor linked with the risk of pre-eclampsia. Other serum/plasma components related to the risk of pre-eclampsia were also measured. Between 12 and 35 weeks, whole-blood Se concentration increased significantly in the Se-treated group but decreased significantly in the placebo group. At 35 weeks, significantly higher concentrations of whole-blood Se and plasma SEPP1 were observed in the Se-treated group than in the placebo group. In line with our hypothesis, the concentration of sFlt-1 was significantly lower at 35 weeks in the Se-treated group than in the placebo group in participants in the lowest quartile of Se status at baseline (P= 0·039). None of the secondary outcome measures was significantly affected by treatment. The present finding that Se supplementation has the potential to reduce the risk of pre-eclampsia in pregnant women of low Se status needs to be validated in an adequately powered trial.
Morgan SB, Graham SP, Salguero FJ, Sánchez Cordón PJ, Mokhtar H, Rebel JMJ, Weesendorp E, Bodman-Smith KB, Steinbach F, Frossard JP (2013) Increased pathogenicity of European porcine reproductive and respiratory syndrome virus is associated with enhanced adaptive responses and viral clearance, Veterinary Microbiology 163 (1-2) pp. 13-22
Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important diseases of swine worldwide. Since its first emergence in 1987 the PRRS virus (PRRSV) has become particularly divergent with highly pathogenic strains appearing in both Europe and Asia. However, the underlying mechanisms of PRRSV pathogenesis are still unclear. This study sets out to determine the differences in pathogenesis between subtype 1 and 3 strains of European PRRSV (PRRSV-I), and compare the immune responses mounted against these strains. Piglets were infected with 3 strains of PRRSV-I: Lelystad virus, 215-06 a British field strain and SU1-bel from Belarus. Post-mortem examinations were performed at 3 and 7 days post-infection (dpi), and half of the remaining animals in each group were inoculated with an Aujeszky's disease (ADV) vaccine to investigate possible immune suppression resulting from PRRSV infection. The subtype 3 SU1-bel strain displayed greater clinical signs and lung gross pathology scores compared with the subtype 1 strains. This difference did not appear to be caused by higher virus replication, as viraemia and viral load in broncho-alveolar lavage fluid (BALF) were lower in the SU1-bel group. Infection with SU1-bel induced an enhanced adaptive immune response with greater interferon (IFN)-³ responses and an earlier PRRSV-specific antibody response. Infection with PRRSV did not affect the response to vaccination against ADV. Our results indicate that the increased clinical and pathological effect of the SU1-bel strain is more likely to be caused by an enhanced inflammatory immune response rather than higher levels of virus replication. © 2012.
Singleton H, graham SP, Bodman-Smith KB, Frossard JP, Steinbach F (2016) Establishing porcine monocyte-derived macrophage and dendritic cell systems for studying the interaction with PRRSV-1, Frontiers in Microbiology Frontiers Media
Monocyte-derived macrophages (MoMØ) and monocyte-derived dendritic cells (MoDC) are two model systems well established in human and rodent systems that can be used to study the interaction of pathogens with host cells. Porcine reproductive and respiratory syndrome virus (PRRSV) is known to infect myeloid cells, such as macrophages (MØ) and dendritic cells (DC). Therefore, this study aimed to establish systems for the differentiation and characterization of MoMØ and MoDC for subsequent infection with PRRSV-1.
M-CSF differentiated monocyte-derived macrophages (MoMØ) were stimulated with activators for classical (M1) or alternative (M2)
activation. GM-CSF and IL-4 generated monocyte-derived dendritic cells (MoDC) were activated with the well established maturation cocktail containing PAMPs and cytokines. In addition, MoMØ and MoDC were treated with dexamethasone and IL-10, which are known immuno-suppressive reagents. Cells were characterized by morphology, phenotype and function and porcine MØ subsets highlighted some divergence from described human counterparts, while MoDC, appeared more similar to mouse and human DCs.
The infection with PRRSV-1 strain Lena demonstrated different replication kinetics between MoMØ and MoDC and within subsets of
each cell type. While MoMØ susceptibility was significantly increased by dexamethasone and IL-10 with an accompanying increase in
CD163/CD169 expression, MoDC supported only a minimal replication of PRRSV These findings underline the high variability in the
susceptibility of porcine myeloid cells towards PRRSV-1 infection.
Beeton L, Khwaja H, Bodman-Smith K, Ferns G, Green F (2006) Genetic variation in the interleukin-6 promoter influences the macrophage inflammatory response, Vascular Pharmacology 45
Shams S, Shafi S, Bodman-Smith K, Williams P, Mehta S, Ferns GA (2008) Anti-heat shock protein-27 (Hsp-27) antibody levels in patients with chest pain: Association with established cardiovascular risk factors, CLINICA CHIMICA ACTA 395 (1-2) pp. 42-46 ELSEVIER SCIENCE BV
Shebaby WN, El-Sibai M, Bodman-Smith K, Karam MC, Mroueh M, Daher CF (2013) The antioxidant and anticancer effects of wild carrot oil extract, Phytotherapy Research 27 (5) pp. 737-744
Daucus carota L. ssp. carota (Apiacea) is used in traditional medicine in Lebanon and in different regions throughout the world. The present study investigates the in vitro anticancer activities of Daucus carota oil extract (DCOE) on four human cancer cell lines as well as its in vitro antioxidant activity. DCOE was extracted from the dried umbels with 50:50 acetone-methanol. The oil extract was analyzed by gas chromatography-mass spectrometry and screened for its antioxidant properties in vitro using 1,1-diphenyl-2-picryl hydrazyl free radical scavenging assay (DPPH), ferrous ion chelating assay (FIC) and the ferric reducing antioxidant power assay (FRAP). The anticancer activity of the oil extract against human colon (HT-29, Caco-2) and breast (MCF-7, MDA-MB-231) cancer cell lines was evaluated using the trypan blue exclusion method and the WST-1 cell proliferation assay. DCOE exhibited antioxidant activity in all assays used. The FRAP value was 164 ± 5.5 ¼mol FeSO4/g, and the IC50 values for DPPH and FIC assays were 2.1 ± 0.03 mg/ml and 0.43 ± 0.02 mg/ml, respectively. Also, DCOE demonstrated a significant increase in cell death and decrease in cell proliferation. The effect of DCOE on the cell lines exhibited time and dose-dependent responses. The present study established that DCOE possesses both antioxidant and promising anticancer activities. Copyright © 2012 John Wiley & Sons, Ltd.
Karam MC, Merckbawi R, El-Kouba JE, Bazzi SI, Bodman-Smith KB (2013) In Leishmania major-induced inflammation, interleukin-13 reduces hyperalgesia, down-regulates IL-1² and up-regulates IL-6 in an IL-4 independent mechanism1This project was mainly funded by the Balamand Research Grant, Experimental Parasitology 134 (2) pp. 200-205
Infection with high dose Leishmania major induces a sustained hyperalgesia in BALB/c mice while low dose induces a short lived hyperalgesia both accompanied with the upregulation of IL-1² and IL-6. Although IL-13 was shown to reduce the high dose L. major hyperalgesia during the treatment period, this effect was accompanied by a significant decrease in the levels of IL-1² and a significant increase in the levels of IL-6 in the paws of mice even beyond this period. Those results suggest that IL-13 exerts those effects via the induction of another mediator, IL-4 being a potential candidate due to its known hypoalgesic effects in other models and to its close functional closeness to IL-13 especially at the level of receptors. In this study we correlated the pain thresholds and the levels of IL-1², IL-6 and IL-4 with the period of IL-13 treatment and beyond it in mice infected with high and low dose of L. major. The results of both models show that IL-1² plays no direct role in provoking the observed hyperalgesia after stopping the treatment with IL-13 which is in contrary to IL-6 which might be a key player after the treatment period. Furthermore we demonstrate that there is no correlation between the levels of IL-4, hyperalgesia, the decreased IL-1² levels and the increased levels of IL-6 in the paws of IL-13 treated and L. major (high and low dose) infected BALB/c mice. © 2013 Elsevier Inc.
Nicolaidou V, Stylianou C, Koumas L, Vassiliou GS, Bodman-Smith KB, Costeas P (2015) Gene expression changes in HLA mismatched mixed lymphocyte cultures reveal genes associated with allorecognition, Tissue Antigens 85 (4) pp. 267-277
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Human leucocyte antigen (HLA) compatibility is the main factor determining the occurrence of graft-vs-host disease (GVHD) in patients. It has also been shown that minor histocompatibility antigen differences as well as genetic polymorphisms that are not sequenced by standard methodology for HLA typing can play a role. We used mixed lymphocyte cultures (MLCs) as a functional cellular test and investigated gene expression changes driven by HLA incompatibility in an effort to better understand the mechanisms involved in the disease. Gene expression profile of HLA matched and HLA mismatched MLC identified differentially regulated genes and pathways. We found that a great number of genes related to immune function were differentially regulated; these genes were also found to be associated with GVHD and graft rejection. The majority of differentially regulated genes were interferon-gamma (IFN³)-inducible genes and IFN³ neutralisation in MLCs abrogated their induction. The microRNA-155, a recently identified target for acute GVHD (aGVHD), was also found to be significantly induced in HLA mismatched MLC but not in the matched setting and its induction was not diminished by blocking IFN³. In this proof-of-principle study we show gene expression changes in mismatched MLC that represent alloreactive responses, correlate with markers involved in GVHD and can potentially be useful in the study of the biological processes involved in this disease.
Shebaby WN, Daher CF, El-Sibai M, Bodman-Smith K, Mansour A, Karam MC, Mroueh M (2015) Antioxidant and hepatoprotective activities of the oil fractions from wild carrot (Daucus carota ssp. carota)., Pharm Biol 53 (9) pp. 1285-1294
CONTEXT: Wild carrot, Daucus carota L. ssp. carota (Apiacae), is widely distributed throughout the world and has various uses in traditional medicine in Lebanon. OBJECTIVE: The present study aimed to fractionate and analyze the chemical composition of the Daucus carota oil extract (DCOE) fractions and to evaluate their antioxidant and hepatoprotective properties in vitro and in vivo. MATERIALS AND METHODS: DCOE was chromatographed on silica gel column to produce four fractions: pentane (F1), 50:50 pentane:diethyl ether (F2), diethyl ether (F3), and 93:7 chloroform: methanol (F4). Qualitative and quantitative analyses of oil fractions were performed by GC-MS and HPLC techniques. The in vitro antioxidant properties were assessed using DPPH, FIC, and ferric-reducing antioxidant power (FRAP) assays. The hepatoprotective property was determined by examining the levels of serum markers (alanine transaminase (ALT) and aspartate transaminase (AST)) and hepatic antioxidant (superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST)) enzymes in CCl4-intoxicated mice pretreated with intraperitoenal 50, 100, or 200 mg/kg b.w. of the oil fractions for 5 d. RESULTS: GCMS analysis of F2 revealed the presence of 2-himachalen-6-ol (61.4%) which is reported for the first time in Daucus carota species. F3 and F4 were rich in phenolics and flavonoids and demonstrated significant DPPH activity (IC50 = 0.29 and 0.38 mg/ml, respectively) and high FRAP values (225.11 and 437.59 µmol FeSO4/g, respectively). The sesquiterpene-rich fraction F1 had the highest FIC ability (IC50 = 0.28 mg/ml). Pretreatment with F1 and F4 reversed the CCl4-induced decrease in SOD, CAT, and GST levels and reduced significantly hepatic damage. DISCUSSION AND CONCLUSION: The current results suggested that wild carrot oil fractions exhibited a unique chemical composition and possessed significant antioxidant activities as well as hepatoprotective effects against CCl4-induced hepatotoxicity.
Beeton L, Tomlin P, Bodman-Smith K, Ferns G, Green F (2006) Inhibitoryeffect of statins on IL6 mRNA expression in THP-1 cells subjected to an inflammatory stimulus, Vascular Pharmacology 45 pp. e16-e17
Franzoni G, Kurkure NV, Edgar DS, Everett HE, Gerner W, Bodman-Smith KB, Crooke HR, Grahama SP (2013) Assessment of the phenotype and functionality of porcine cd8 t cell responses following vaccination with live attenuated classical swine fever virus (CSFV) and virulent CSFV challenge, Clinical and Vaccine Immunology 20 (10) pp. 1604-1616
Vaccination with live attenuated classical swine fever virus (CSFV) induces solid protection after only 5 days, which has been associated with virus-specific T cell gamma interferon (IFN-³) responses. In this study, we employed flow cytometry to characterize T cell responses following vaccination and subsequent challenge infections with virulent CSFV. The CD3 + CD4- CD8hi T cell population was the first and major source of CSFV-specific IFN-³. A proportion of these cells showed evidence for cytotoxicity, as evidenced by CD107a mobilization, and coexpressed tumor necrosis factor alpha (TNF-±). To assess the durability and recall of these responses, a second experiment was conducted where vaccinated animals were challenged with virulent CSFV after 5 days and again after a further 28 days. While virus-specific CD4 T cell (CD3+ CD4+ CD8±+) responses were detected, the dominant response was again from the CD8 T cell population, with the highest numbers of these cells being detected 14 and 7 days after the primary and secondary challenges, respectively. These CD8 T cells were further characterized as CD44hi CD62L- and expressed variable levels of CD25 and CD27, indicative of a mixed effector and effector memory phenotype. The majority of virus-specific IFN-³+ CD8 T cells isolated at the peaks of the response after each challenge displayed CD107a on their surface, and subpopulations that coexpressed TNF-± and interleukin 2 (IL-2) were identified. While it is hoped that these data will aid the rational design and/or evaluation of next-generation marker CSFV vaccines, the novel flow cytometric panels developed should also be of value in the study of porcine T cell responses to other pathogens/vaccines. Copyright © 2013, American Society for Microbiology. All Rights Reserved.
Shebaby WN, Bodman-Smith KB, Mansour A, Mroueh M, Taleb RI, El-Sibai M, Daher CF (2015) Daucus carota Pentane-Based Fractions Suppress Proliferation and Induce Apoptosis in Human Colon Adenocarcinoma HT-29 Cells by Inhibiting the MAPK and PI3K Pathways, JOURNAL OF MEDICINAL FOOD 18 (7) pp. 745-752 MARY ANN LIEBERT, INC
Shebaby WN, Mroueh M, Bodman-Smith K, Mansour A, Taleb RI, Daher CF, El-Sibai M (2014) Daucus carota pentane-based fractions arrest the cell cycle and increase apoptosis in MDA-MB-231 breast cancer cells., BMC Complement Altern Med 14
BACKGROUND: Daucus carota L.ssp.carota (wild carrot), an herb used in folk medicine worldwide, was recently demonstrated to exhibit anticancer activity. In this study we examined the anticancer effect of Daucus carota oil extract (DCOE) fractions on the human breast adenocarcinoma cell lines MDA-MB-231 and MCF-7 and clarified the mechanism of action. METHODS AND RESULTS: Using the WST assay, the pentane fraction (F1) and 1:1 pentane:diethyl ether fraction (F2) were shown to possess the highest cytotoxicity against both cell lines. Flow cytometric analysis revealed that both fractions induced the accumulation of cells in the sub-G1 phase, increase in apoptotic cell death and chromatin condensation. The increase in apoptosis in response to treatment was also apparent in the increase in BAX and the decrease in Bcl-2 levels as well as the proteolytic cleavage of both caspase-3 and PARP as revealed by Western blot. Furthermore, treatment of MDA-MB-231 cells with either fraction significantly reduced the level of phosphorylated Erk but did not show any effect on phosphorylated Akt. The combined treatment with a potent PI3K inhibitor (wortmannin) and F1 or F2 fraction had a synergistic inhibitory effect on cell survival which shows that these two drugs work on different pathways. CONCLUSIONS: These results suggest that the pentane-based fractions of DCOE possess potential anti-cancer activity that is mainly mediated through the Erk pathway.
Beeton L, Khwaja H, Bodman-Smith K, Ferns G, Green F (2006) Interleukin-6 promoter polymorphisms influence the inter-individual macrophage inflammatory response, ATHEROSCLEROSIS SUPPLEMENTS 7 (3) pp. 289-289 ELSEVIER IRELAND LTD
Casey R, McFadden J, Newcombe J, Bodman-Smith M, Bodman-Smith K (2007) C-reactive protein binds to Neisseria meningitidis and affects macrophage responses to infection, IMMUNOLOGY 120 pp. 20-20 BLACKWELL PUBLISHING
Kaminska E, Bodman-Smith K, Coulton G, Dalgleish A, Bodman-Smith MD (2011) Identification of putative biomarkers in cancer therapy, IMMUNOLOGY 135 pp. 121-121
Karam MC, Hamdan HG, Abi Chedid NA, Baroody GM, Bodman-Smith KB, Eales-Reynolds L-JE (2006) Leishmania major: Low infection dose causes short-lived hyperalgesia and cytokines upregulation in mice, Experimental Parasitology 113 (3) pp. 168-173
Neural involvement was traditionally associated with leprosy. However, more recent studies have shown the presence of a persistent hyperalgesia in cutaneous leishmaniasis caused by the infection of BALB/c mice with a high dose of Leishmania major. In this study, we report the presence of hyperalgesia within the first two weeks of infection caused by a low dose of the parasite. Using BALB/c mice, we demonstrate the presence of hyperalgesia during the first 10 days of infection as assessed by thermal pain tests. After 10 days these decreased pain thresholds start to recover resulting in similar levels to those in uninfected controls during the third week of infection. This hyperalgesia is accompanied by a sustained upregulation of interleukin-1² (IL-1²) and an early upregulation of interleukin-6 (IL-6) which is restored to normal levels after five days of infection. In conclusion, this study shows that, during early infection, the low dose of L. major causes hyperalgesia accompanied by an upregulation of IL-1² and IL-6 and that these effects are reversed within the first two weeks of infection. © 2006 Elsevier Inc. All rights reserved.
AlHomidani H, Bodman-Smith K, Agouni A, Green FR (2014) GENETICS OF INTERLEUKIN 6 AND SELENOPROTEIN S THAT HAVE A ROLE IN INFLAMMATION AND CORONARY ARTERY DISEASE, ATHEROSCLEROSIS 237 (2) pp. E3-E3 ELSEVIER IRELAND LTD
Shebaby W, El-Sibai M, Mroueh M, Bodman-Smith K, Taleb R, Daher C (2014) Hepatoprotective activity of the wild carrot chloroform-based fraction against CCl4-induced liver toxicity in mice, PLANTA MEDICA 80 (16) pp. 1523-1524 GEORG THIEME VERLAG KG
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
Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important diseases of swine worldwide. Since its first emergence in 1987 the PRRS virus (PRRSV) has become particularly divergent with highly pathogenic strains appearing in both Europe and Asia. However, the underlying mechanisms of PRRSV pathogenesis are still unclear. This study sets out to determine the differences in pathogenesis between subtype 1 and 3 strains of European PRRSV (PRRSV-I), and compare the immune responses mounted against these strains. Piglets were infected with 3 strains of PRRSV-I: Lelystad virus, 215-06 a British field strain and SU1-bel from Belarus. Post-mortem examinations were performed at 3 and 7 days post-infection (dpi), and half of the remaining animals in each group were inoculated with an Aujeszky's disease (ADV) vaccine to investigate possible immune suppression resulting from PRRSV infection. The subtype 3 SU1-bel strain displayed greater clinical signs and lung gross pathology scores compared with the subtype 1 strains. This difference did not appear to be caused by higher virus replication, as viraemia and viral load in broncho-alveolar lavage fluid (BALF) were lower in the SU1-bel group. Infection with SU1-bel induced an enhanced adaptive immune response with greater interferon (IFN)-³ responses and an earlier PRRSV-specific antibody response. Infection with PRRSV did not affect the response to vaccination against ADV. Our results indicate that the increased clinical and pathological effect of the SU1-bel strain is more likely to be caused by an enhanced inflammatory immune response rather than higher levels of virus replication. Crown Copyright © 2012.
Vaccination with live attenuated classical swine fever virus (CSFV) vaccines induces a rapid onset of protection which has been associated with virus-specific CD8 T cell IFN-³ responses. In this study, we assessed the specificity of this response, by screening a peptide library spanning the CSFV C-strain vaccine polyprotein to identify and characterise CD8 T cell epitopes. Synthetic peptides were pooled to represent each of the 12 CSFV proteins and used to stimulate PBMC from four pigs rendered immune to CSFV by C-strain vaccination and subsequently challenged with the virulent Brescia strain. Significant IFN-³ expression by CD8 T cells, assessed by flow cytometry, was induced by peptide pools representing the core, E2, NS2, NS3 and NS5A proteins. Dissection of these antigenic peptide pools indicated that, in each instance, a single discrete antigenic peptide or pair of overlapping peptides was responsible for the IFN-³ induction. Screening and titration of antigenic peptides or truncated derivatives identified the following antigenic regions: core241-255 PESRKKLEKALLAWA and NS31902-1912 VEYSFIFLDEY, or minimal length antigenic peptides: E2996-1003 YEPRDSYF, NS21223-1230 STVTGIFL and NS5A3070-3078 RVDNALLKF. The epitopes are highly conserved across CSFV strains and variable sequence divergence was observed with related pestiviruses. Characterisation of epitope-specific CD8 T cells revealed evidence of cytotoxicity, as determined by CD107a mobilisation, and a significant proportion expressed TNF-± in addition to IFN-³. Finally, the variability in the antigen-specificity of these immunodominant CD8 T cell responses was confirmed to be associated with expression of distinct MHC class I haplotypes. Moreover, recognition of NS 21223-1230 STVTGIFL and NS31902-1912 VEYSFIFLDEY by a larger group of C-strain vaccinated animals showed that these peptides could be restricted by additional haplotypes. Thus the antigenic regions and epitopes identified represent attractive targets for evaluation of their vaccine potential against CSFV. © 2013 Franzoni et al.
Ogbechi J, Ruf M-T, Hall BS, Bodman-Smith K, Vogel M, Wu H-L, Stainer A, Esmon CT, Ahnstroem J, Pluschke G, Simmonds RE (2015) Mycolactone-Dependent Depletion of Endothelial Cell Thrombomodulin Is Strongly Associated with Fibrin Deposition in Buruli Ulcer Lesions, PLOS PATHOGENS 11 (7) ARTN e1005011 PUBLIC LIBRARY SCIENCE
Shahidi M, Powell L, Oviedo-Orta E, Bodman-Smith K (2009) Incubation of endothelial cells with CRP results in alterations in surface Fc gamma RI expression, Journal of Thrombosis and Haemostasis 7
Singleton H, Frossard J-P, Bodman-Smith KB, Graham SP, Steinbach F (2011) The effect of cytokines on porcine monocytes and alveolar macrophages, IMMUNOLOGY 135 pp. 90-90
Bodman-Smith K, Gregory RE, Harrison PT, Raynes JG (2004) Fc³RIIa expression with Fc³RI results in C-reactive protein and IgG-mediated phagocytosis, Journal of Leukocyte Biology 75 pp. 1029-1035
Singleton H, Everett H, Graham S, Bodman-Smith K, Steinbach F (2013) Characterisation of porcine monocytes, macrophages and dendritic cells, IMMUNOLOGY 140 pp. 122-122 WILEY-BLACKWELL
Karam MC, Al-Kouba JE, Bazzi SJ, Smith CB, Leung L (2011) Interleukin-13 reduces hyperalgesia and the level of interleukin-1² in BALB/c mice infected wioth Leishmania major with an upregulation of interleukin-6, Journal of Neuroimmunology 234 pp. 49-54 Elsevier
Sosan O, Graham S, Everett H, Crudgington B, Bodman-Smith K, Crooke H (2012) Differential antiviral effect of porcine interferon alpha subtypes on classical swine fever virus infection of porcine monocytes, CYTOKINE 59 (3) pp. 552-552 ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Muirhead N, M'Shahidi M, Al'Mushtaq R, Lodge J, Frost G, Bodman-Smith K (2009) Do short chain fatty acids have an anti-inflammatory and vascular protective effect on endothelial cells?, Cereal Foods World 54
Jenson JS, Casey R, Newcombe J, Smith M, McFadden JJ, Bodman-Smith K (2008) Dendritic cell responses to C-reactive protein-opsonised Neisseria meningitidis, IMMUNOLOGY 125 pp. 124-124 WILEY-BLACKWELL PUBLISHING, INC
Casey R, Newcombe J, McFadden J, Bodman-Smith KB (2008) The acute-phase reactant C-reactive protein binds to phosphorylcholine-expressing Neisseria meningitidis and increases uptake by human phagocytes, INFECTION AND IMMUNITY 76 (3) pp. 1298-1304 AMER SOC MICROBIOLOGY
Shebaby W, Daher C, El-Sibai M, Bodman-Smith K, Taleb R, Mroueh M (2014) Antioxidant and hepatoprotective activities of the pentane fraction of wild carrot oil, PLANTA MEDICA 80 (16) pp. 1495-1495 GEORG THIEME VERLAG KG
Singleton Helen, Graham Simon P., Frossard Jean-Pierre, Bodman-Smith Katherine B., Steinbach Falko (2018) Infection of monocytes with European porcine reproductive and respiratory syndrome virus (PRRSV-1) strain Lena is significantly enhanced by dexamethasone and IL-10, Virology 517 pp. 199-207 Elsevier
Monocytes are considered refractory to porcine reproductive and respiratory syndrome virus type 1 (PRRSV-1) infection. However, monocytes are only short-lived in blood, being able to differentiate into macrophages and dendritic cells (DC). It was therefore merited to revisit PRRSV-1 interaction with monocytes, particularly those treated with cytokines influencing monocyte biology. Thus, several factors were screened, particularly those modulating monocyte differentiation and expression of putative PRRSV-1 receptors (CD169 and CD163). M-CSF, known to stimulate macrophage differentiation, did not increase their susceptibility to PRRSV-1. Nor did GM-CSF or IL-4, known drivers for monocyte-derived DC (MoDC) differentiation. In contrast, monocyte treatment with IL-10 or the corticosteroid, dexamethasone, known to be potent suppressors of monocyte differentiation, was correlated with increased susceptibility to PRRSV-1 infection. While this effect was strongly correlated to CD163 and CD169 expression, our data suggest that receptor expression is not the only factor driving successful infection of PPRSV-1 in monocytes.