Thioredoxin peroxidase secreted by Echinococcus granulosus induces the alternative activation of macrophages in mice (MPF2P.755)

Abstract

Abstract Alternatively activated macrophages (AAM) are key to promoting Th2 responses and have been associated with a variety of roles during helminth infection. We have shown that E. granulosus infection induces a polarized Th2 response in its intermediate hosts. The role of AAM in the regulation of the immune response is unclear. Here we describe the effects of a thioredoxin peroxidase (TPx) derived from E. granulosus, an enzymatic scavenger of H2O2, on murine macrophage phenotype in vivo and in vitro. The activation status of macrophages was analyzed by evaluating the expression of genetic markers of alternative activation, namely, Fizz1, Ym1, and Arg1. AAMs were recruited to the peritoneum of mice of E. granulosus infection. Administration of hydatid cyst fluid (HCF) and recombinant EgTPx or its inactive recombinant variant (rvEgTPx) also induced the recruitment of AAM to the peritoneum indicated that the immunomodulatory property of EgTPx is not due to its antioxidant activity. In vitro studies showed that HCF and EgTPx or rvEgTPx can directly converts PECs from normal mice to an alternatively activated phenotype characterized by the production of high levels of Arg1. Our data suggest that the Th2 responses induced by the E. granulosus infection are mediated through the secretion of molecules, one of which is EgTPx, that induce the recruitment and alternative activation of macrophages.