Blockade Of PD-1 Signaling Enhances Th2 Cell Responses And Aggravates Liver Immunopathology In Mice With Schistosomiasis Japonica

More than 220 million people worldwide are chronically infected with schistosomes,causing severe disease or even death.The major pathological damage occurring in schistosomiasis is attributable to the granulomatous inflammatory response and liver fibrosis induced by schistosome eggs.The inflammatory response is tightly controlled and parallels immunosuppressive regulation,constantly maintaining immune homeostasis and limiting excessive immunopathologic damage in important host organs.It is well known that the activation of programmed death 1(PD-1)signaling causes a significant suppression of T cell function.However,how PD-1 signaling is regulated in CD4+ T cells and its role in modulating immune responses,particularly the regulation of immunopathology during schistosome infection,has yet to be defined.Here,we show for the first time that PD-1 is up regulated in CD4+T cells in S.japonicum-infected patients,as well as in mouse models.In addition,our in vitro data suggests that parasite egg antigens may be the major factor that promotes the induction of PD-1 expression in CD4+ T cells.Finally,we found that the blockade of PD-1 signaling enhanced CD4+ T helper 2(Th2)cell responses and led to more severe liver immunopathology in mice with S.japonicum infection,without a reduction of egg production or deposition in the host liver.Overall,our study suggests that PD-1 signaling is specifically induced to control Th2-associated inflammatory responses during schistosome infection and is beneficial to the development of PD-1-based control of liver immunopathology.