Gut Microbiota Elicits a Protective Immune Response against Malaria Transmission

Glycosylation processes are under high natural selection pressure, presumably because these can modulate resistance to infection. Here, we asked whether inactivation of the UDP-galactose:β-galactoside-α1-3-galactosyltransferase (α1,3GT) gene, which ablated the expression of the Galα1-3Galβ1-4GlcNAc-R (α-gal) glycan and allowed for the production of anti-α-gal antibodies (Abs) in humans, confers protection against Plasmodium spp. infection, the causative agent of malaria and a major driving force in human evolution. We demonstrate that both Plasmodium spp. and the human gut pathobiont E. coli O86:B7 express α-gal and that anti-α-gal Abs are associated with protection against malaria transmission in humans as well as in α1,3GT-deficient mice, which produce protective anti-α-gal Abs when colonized by E. coli O86:B7. Anti-α-gal Abs target Plasmodium sporozoites for complement-mediated cytotoxicity in the skin, immediately after inoculation by Anopheles mosquitoes. Vaccination against α-gal confers sterile protection against malaria in mice, suggesting that a similar approach may reduce malaria transmission in humans. [Display omitted] [Display omitted] •α-gal is expressed at the surface of Plasmodium sporozoites•Anti-α-gal Abs recognizing E. coli O86:B7 are protective against malaria•Anti-α-gal Abs are cytotoxic to Plasmodium sporozoites•Vaccination against α-gal confers sterile protection against malaria Specific members of the gut microbiota induce antibodies that prevent malaria transmission through recognition of a glycan residue that is shared by the microbiota and the causative agent of malaria, the Plasmodium.