title: Characteristics of IL-17 induction by Schistosoma japonicum infection in C57BL/6 mouse liver.
abstract: Schistosomiasis japonica is a severe tropical disease caused by the parasitic worm Schistosoma japonicum. Among the most serious pathological effects of S. japonicum infection are hepatic lesions (cirrhosis and fibrosis) and portal hypertension. Interleukin-17 (IL-17) is a pro-inflammatory cytokine involved in the pathogenesis of many inflammatory and infectious conditions, including schistosomiasis. We infected C57BL/6 mice with S. japonicum and isolated lymphocytes from the liver to identify cell subsets with high IL-17 expression and release using flow cytometry and ELISA. Expression and release of IL-17 was significantly higher in hepatic lymphocytes from infected mice compared with control mice in response to both non-specific stimulation with anti-CD3 monoclonal antibody plus/anti-CD28 monoclonal antibody and PMA plus ionomycin. We then compared IL-17 expression in three hepatic T-cell subsets, T helper, natural killer T and γδT cells, to determine the major source of IL-17 during infection. Interleukin-17 was induced in all three subsets by PMA + ionomycin, but γδT lymphocytes exhibited the largest increase in expression. We then established a mouse model to further investigate the role of IL-17 in granulomatous and fibrosing inflammation against parasite eggs. Reducing IL-17 activity using anti-IL-17A antibodies decreased infiltration of inflammatory cells and collagen deposition in the livers of infected C57BL/6 mice. The serum levels of soluble egg antigen (IL)-specific IgGs were enhanced by anti-IL-17A monoclonal antibody blockade, suggesting that IL-17 normally serves to suppress this humoral response. These findings suggest that γδT cells are the most IL-17-producing cells and that IL-17 contributes to granulomatous inflammatory and fibrosing reactions in S. japonicum-infected C57BL/6 mouse liver.
authors.affiliation: Department of Pathogenic Biology and Immunology, Guangzhou Medical College, Guangzhou, China.
authors.forename: Dianhui
authors.initials: D
authors.lastname: Chen
authors.forename: Xueping
authors.initials: X
authors.lastname: Luo
authors.forename: Hongyan
authors.initials: H
authors.lastname: Xie
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Gao
authors.forename: Huilong
authors.initials: H
authors.lastname: Fang
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D000913:Antibodies, Protozoan / Q000097:blood; D002478:Cells, Cultured; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006099:Granuloma / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology; D018836:Inflammation Mediators / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D012549:Schistosoma japonicum / Q000276:immunology* / Q000472:pathogenicity; D012554:Schistosomiasis japonica / Q000188:drug therapy / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D058504:Th17 Cells / Q000276:immunology; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000913:Antibodies, Protozoan; D024061:Collagen Type III; C098680:Il17a protein, mouse; D018836:Inflammation Mediators; D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015759:Ionomycin
keywords: Schistosoma japonicum; T helper type 17; interleukin-17; liver; natural killer T cell; γδT cell
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