Gut microbiota elicits a protective immune response against malaria transmission.

Abstract

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.

• Authors: Bahtiyar Yilmaz, Silvia Portugal, Tuan M Tran, Raffaella Gozzelino, Susana Ramos, Joana Gomes, Ana Regalado, Peter J Cowan, Anthony J F d'Apice, Anita S Chong, Ogobara K Doumbo, Boubacar Traore, Peter D Crompton, Henrique Silveira, Miguel P Soares
• Journal: Cell (Cell) Vol. 159 Issue 6 Pg. 1277-89 (Dec 04 2014) ISSN: 1097-4172 [Electronic] United States
• PMID: 25480293 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Bacterial
• Antibodies, Protozoan
• Autoantigens
• Immunoglobulin M
• Polysaccharides
• Toll-Like Receptor 9
• Galactosyltransferases

Topics

• Adult
• Animals
• Anopheles (parasitology)
• Antibodies, Bacterial (blood, immunology)
• Antibodies, Protozoan (blood, immunology)
• Autoantigens (immunology)
• Cell Line, Tumor
• Child
• Escherichia coli (classification, immunology, physiology)
• Female
• Galactosyltransferases (genetics, metabolism)
• Gastrointestinal Tract (microbiology)
• Germ-Free Life
• Humans
• Immunoglobulin M (blood, immunology)
• Malaria, Falciparum (immunology, microbiology, parasitology, transmission)
• Mice
• Plasmodium (classification, growth & development, immunology, physiology)
• Plasmodium falciparum (immunology, physiology)
• Polysaccharides (immunology)
• Sporozoites (immunology)
• Toll-Like Receptor 9 (agonists)