Schistosoma mansoni cercarial invadolysin cleaves complement C3 and suppresses proinflammatory cytokine production

Abstract

Schistosoma mansoni employs immune evasion and immunosuppression to overcome immune responses mounted by its snail and human hosts. Myriad immunomodulating factors underlie this process, some of which are proteases. Here, we demonstrate that one protease, an invadolysin we have termed SmCI-1, is released from the acetabular glands of S. mansoni cercaria and is involved in creating an immunological milieu favorable for survival of the parasite. We confirm the presence of SmCI-1 in the cercarial stage of S. mansoni and demonstrate that it is released during transformation into the schistosomula. We confirm SmCI-1 functions as a metalloprotease with the capacity to cleave collagen type IV, gelatin and fibrinogen. We also show that complement component C3b is cleaved by this protease, resulting in inhibition of the classical and alternative complement pathways. Finally, we assess the effect of SmCI-1 on cytokine release from human peripheral blood mononuclear cells, providing compelling evidence that SmCI-1 promotes an anti-inflammatory microenvironment by enhancing production of IL-10 and suppressing the production of inflammatory cytokines like IL-1B and IL-12p70 and those involved in eosinophil recruitment and activation, like eotaxin-1 and IL-5.