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Characteristics of IL ‐17 induction by S chistosoma japonicum infection in C57 BL /6 mouse liver
Author(s) -
Chen Dianhui,
Luo Xueping,
Xie Hongyan,
Gao Zhiyan,
Fang Huilong,
Huang Jun
Publication year - 2013
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12105
Subject(s) - biology , schistosoma japonicum , immunology , cytokine , interleukin 17 , monoclonal antibody , inflammation , antibody , t cell , antigen , immune system , schistosomiasis , helminths
Summary S chistosomiasis japonica is a severe tropical disease caused by the parasitic worm S chistosoma japonicum . Among the most serious pathological effects of S . japonicum infection are hepatic lesions (cirrhosis and fibrosis) and portal hypertension. I nterleukin‐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.