Host-Specific Serum Factors Control the Development and Survival of Schistosoma mansoni

Introduction Schistosomiasis is a neglected tropical disease (NTD) caused by blood-dwelling flatworms which develop from skin-penetrating cercariae, the freely swimming water-borne infective stage ofSchistosoma mansoni, into adult worms. This natural course of infection can be mimicked in experimental mouse models of schistosomiasis. However, only a maximum of 20-30% of penetrated cercariae mature into fecund adults. The reasons for this are unknown but could potentially involve soluble factors of the innate immune system, such as complement factors and preexisting, natural antibodies. Materials and Methods Using our recently developed novel serum- and cell-freein vitroculture system for newly transformed schistosomula (NTS), which supports long-term larval survival, we investigated the effects of mouse serum and its major soluble complement factors C1q, C3, C4 as well as preexisting, natural IgMin vitroand assessed worm developmentin vivoby infecting complement and soluble (s)IgM-deficient animals. Results In contrast to sera from humans and a broad variety of mammalian species, serum from mice, surprisingly, killed parasites already at skin stagein vitro. Interestingly, the most efficient killing component(s) were heat-labile but did not include important members of the perhaps best known family of heat-labile serum factors, the complement system, nor consisted of complement-activating natural immunoglobulins. Infection of complement C1q and sIgM-deficient mice withS. mansonias well asin vitrotests with sera from mice deficient in C3 and C4 revealed no major role for these soluble factorsin vivoin regard to parasite maturation, fecundity and associated immunopathology. Rather, the reduction of parasite maturation from cercariae to adult worms was comparable to wild-type mice. Conclusion This study reveals that not yet identified heat-labile serum factors are major selective determinants of the host-specificity of schistosomiasis, by directly controlling schistosomal development and survival.