Leishmaniagenetic exchange is mediated by IgM natural antibodies

Host factors that mediate Leishmaniagenetic exchange are not well defined. Here we demonstrate that natural IgM (IgMn)1–4antibodies mediate parasite genetic exchange by inducing the transient formation of a spherical parasite clump that promotes parasite fusion and hybrid formation. We establish that IgMn from Leishmania-free animals binds to the surface of Leishmaniaparasites to induce significant changes in the expression of parasite transcripts and proteins. Leishmaniabinding to IgMn is partially lost after glycosidase treatment, although parasite surface phosphoglycans, including lipophosphoglycan, are not required for IgMn-induced parasite clumping. Notably, the transient formation of parasite clumps is essential for Leishmaniahybridization in vitro. In vivo, we observed a 12-fold increase in hybrid formation in sand flies provided a second blood meal containing IgMn compared with controls. Furthermore, the generation of recombinant progeny from mating hybrids and parental lines were only observed in sand flies provided with IgMn. Both in vitro and in vivo IgM-induced Leishmaniacrosses resulted in full genome hybrids that show equal patterns of biparental contribution. Leishmaniaco-option of a host natural antibody to facilitate mating in the insect vector establishes a new paradigm of parasite–host–vector interdependence that contributes to parasite diversity and fitness by promoting genetic exchange.