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The Correlation and the Mechanism of the Severity of Host Liver Pathogenesis and the Level of Serum SjHSP60Antibody

Author: ChenXiaoJun
Tutor: SuChuan
School: Nanjing Medical University
Course: Pathogen Biology
Keywords: Schistosoma japonicum Liver pathology HSP60 Antibodies Tfh cells Macrophages ICOSL
CLC: R532.21
Type: PhD thesis
Year: 2013
Downloads: 26
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Abstract


Schistosomiasis remains a major public health problem in many developing countries in tropical and subtropical regions. Much of the symptomatology of schistosomiasis is attributed to the egg-induced granulomatous inflammatory response and associated fibrosis, which are the primary causes of morbidity in infected individuals and in some cases will ultimately be lethal. Yet it is still a better outcome for both parasite and its hosts than the alternative of pervasive liver tissue damage caused by unsequestered egg toxins. Evaluation of the pathogenic level of hepatic fibrosis and understanding the mechanism of granuloma formation are crucial for better schistomiasis treatment.This study was performed to determine whether the level of antibody to Schistosoma japonicum heat shock protein60(SjHSP60) could be associated with the extent of the hepatic fibrosis in infected mice, rabbits and patients. We found that the titers of total IgG and the subtype IgG1anti-SjHSP60antibodies in infected mice, rabbits and human patients were significantly higher than that of the controls., and the titers of total IgG and the subtype IgG1anti-SjHSP60antibodies were positively correlated with the extent of hepatic pathology in infected mice, rabbits and patients. Furthermore, the grades of collagen III and a-SMA, but not collagen I expression were positively associated with the level of serum SjHSP60IgG antibody in infected rabbits compared to the controls. Moreover, the titer of total IgG anti-SjHSP60antibody in infected mice with CCl4was higher than that of the infected mice without CCl4, although little change in the level of SjHSP60IgGl antibody was detected in infected mice treated with or without CCl4. These data suggest that SjHSP60antibody has diagnostic and prognostic utility for progression in schistosomiasis.However, the mechanisms underlying the correlation of the level of SjHSP60antibody with the extent of hepatic fibrosis in schistosomiasis remain unknown. To address this issue, we infected ICOSL KO mice with S. japonicum. We found that Tfh cells play a central role in the production of Sj HSP60antibody during infection. Furthermore, we for the first time showed that follicular helper T (Tfh) cells are recruited to the liver to upregulate hepatic granuloma formation during S.japonicum infection, and identified a novel function of macrophages in Tfh cells induction. In addition, our results showed that the generation of Tfh cells driven by macrophages is dependent on cell-cell contact and the level of costimulator ligand (ICOSL) on macrophages which is regulated by CD40-CD40L signaling.Our findings indicated that SjHSP60IgG and IgGl antibody levels were positively correlated with the extent of hepatic fibrosis and that the level of SjHSP60antibody may be biomarkers for the evaluation of the pathogenic level of hepatic fibrosis in Schistosoma japonicum-infected patients and uncovered a previously unappreciated role of Tfh cells in liver pathogenesis in schistosomiasis and macrophages in Tfh cell differentiation, which contributes to a deeper understanding and may help to design better treatment of the schistosomiasis.

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CLC: > Medicine, health > Internal Medicine > Parasitic diseases > Helminthiasis > Trematodes > Schistosomiasis
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