Abstract
The major pathological changes during Schistosoma J. infection are characterized by granulomatous inflammation in the liver, a cellular immune response to schistosomal egg antigens. The molecular mechanisms initiating or promoting this schistosomal granulomatous inflammation remain poorly understood. In the present study, we first demonstrated that in mice infected with Schistosoma J. for 6 weeks exhibited increased levels of IL-1β in liver, a major product of NLRP3 inflammasomes and collagen deposition around the eosinophilic granuloma with Schistosoma J. eggs, which was substantially attenuated by caspase-1 inhibitor, YVAD. This activation of the NLRP3 inflammasome occurred in hepatic stellate cells (HSCs), as shown by a marked increase in co-localization of IL-1β with HSCs marker, desmin. Using isolated, cultured mouse HSCs, we further explored the mechanisms by which soluble egg antigen (SEA) from Schistosoma J. activates NLRP3 inflammasomes. SEA induced the formation and activation of NLRP3 inflammasomes, which was associated with both redox regulation and lysosomal dysfunction, but not with potassium channel activation. These results suggest that NLRP3 inflammasome activation in HSCs may serve as an early mechanism to turn on the inflammatory response and thereby instigate liver fibrosis during Schistosoma J infection.