Toll-like receptor-2 regulates macrophage polarization induced by excretory-secretory antigens from Schistosoma japonicum eggs and promotes liver pathology in murine schistosomiasis

Schistosomiasis is endemic to many regions of the world and affects approximately 200 million people.Conventional adaptive T cell responses are considered to be the primary contributors to the pathogenesis of Schistosoma japonicum infection, leading to liver granuloma and fibrosis.However, the functional polarization of macrophages and the associated underlying molecular mechanisms during the pathogenesis of schistosomiasis remains unknown.In the present study, we found that excretory-secretory (ES) antigens derived from S. japonicum eggs can activate macrophages, which exhibit an M2b polarization.Furthermore, ES antigen-induced M2b polarization was found to be dependent on enhanced NF-κB signaling mediated by the MyD88/MAPK pathway in a TLR2-dependent manner.In addition, the cytokine profile of the liver macrophages from wild-type-infected mice are quite distinct from those found in TLR2 knockout-infected mice by quantitative PCR analysis.More importantly, the size of granuloma and the severity of the fibrosis in the livers of TLR2 -/-mice were significantly reduced compared to that in WT mice.Our findings reveal a novel role for M2b polarization in the pathogenesis of schistosome infection. Author summarySchistosomiasis is a global health concern that affects primarily tropical and subtropical areas.During a schistosome infection, the eggs are trapped in the host liver and products derived from eggs induce a polarized Th2 response, resulting in granuloma formation and eventually fibrosis.Thus, it is important to elucidate the mechanism of granuloma formation and fibrosis development.Here, we show that activated macrophages play a novel role in the promotion of hepatic granuloma formation and liver fibrosis in a Schistosoma