Gut Microbiota Elicits a Protective Immune Response against Malaria Transmission

Bahtiyar Yilmaz

Silvia Portugal

Tuan M. Tran

Raffaella Gozzelino

Open Access

DOI: http://dx.doi.org/10.1016/j.cell.2014.10.053

Open access funded by European Research Council

Highlights

•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

Summary

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 bothPlasmodium 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 Plasmodiumsporozoites 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.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

Received: August 8, 2014; Received in revised form: September 26, 2014; Accepted: September 30, 2014;