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Cell. 2014 Dec 4;159(6):1277-89. doi: 10.1016/j.cell.2014.10.053.

Gut microbiota elicits a protective immune response against malaria transmission.

Author information

  • 1Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal.
  • 2Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Twinbrook II, Room 125, 12441 Parklawn Drive, Rockville, MD 20852-8180, USA.
  • 3Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal; Centro de Malaria e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira, 100, 1349-008 Lisboa, Portugal.
  • 4Immunology Research Centre, St. Vincent's Hospital, Fitzroy, Melbourne, VIC 3065, Australia; Department of Medicine, University of Melbourne, Parkville, VIC 2900, Australia.
  • 5Section of Transplantation, Department of Surgery, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
  • 6Mali International Center of Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, 1805 Bamako, Mali.
  • 7Centro de Malaria e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira, 100, 1349-008 Lisboa, Portugal.
  • 8Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal. Electronic address: mpsoares@igc.gulbenkian.pt.

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.

Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

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PMID:
25480293
[PubMed - indexed for MEDLINE]
PMCID:
PMC4261137
Free PMC Article
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