The Role And Mechanism Of Aquaporin 4 In The Immunity Of Schistosoma Japonicum Infection

Schistosomiasis is a chronic parasitic disease that affects approximately 200 million people.In Schistosomiasis japonica and mansoni,parasite eggs trapped in host liver and stimulated the host immune responses to form the granulomas.Severe granulomatous responses subsequently result in more serious liver fibrosis and circulatory impairment.Thus,elucidation of the mechanisms of these responses will not only help designing new therapies to control granuloma-associated immunopathology but also support the vaccine development.The role of aquaporin-4(AQP4)in water transport has been extensively investigated in the central nervous system(CNS).Recently,studies have shown that AQP4 expresses in immune system and lack of AQP4 in mice results in significantly less Treg cells under physiological condition.However,little information exists regarding its contribution to the immune responses in schistosome infection.In this study,we investigated the possible role of AQP4 in immune responses in schistosome infection by comparison of the differences in various CD4+ T subsets responses,including Th1,Th2,Th17,and CD4+CD25+ T regulatory cells(Tregs)responses,between schistosome-infected AQP4(knockout)KO mice and its wild-type(WT)littermates.Results showed an enhanced Th2 but reduced Thl and Treg responses in AQP4 KO mice with Schistosomiasis japonica.These dysregulated immune responses lead to an enhanced graunulomatous response and the increased accumulation of eosinophils and macrophages around eggs in the host liver.We further found that macrophages from AQP4 KO mice expressed more c-maf,which upregulate the secretion of IL-4 upon SEA stimulation,which may account for the enhanced Th2 cell response in schistosome-infected AQP4 KO mice.Our data for the first time provide primary evidences that AQP4 plays an important role in immune regulation in schistosomiasis.Our findings contribute not only to the development of AQP4-based interventions to restrain immunopathology in schistosomiasisbut also tobetter understanding of the immunity to schistosome infection.