Journal article
Gut microbiota elicits a protective immune response against malaria transmission
B Yilmaz, S Portugal, TM Tran, R Gozzelino, S Ramos, J Gomes, A Regalado, PJ Cowan, AJF D'Apice, AS Chong, OK Doumbo, B Traore, PD Crompton, H Silveira, MP Soares
Cell | Published : 2014
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 transmiss..
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Awarded by European Commission
Funding Acknowledgements
The authors thank the Inflammation Group (IGC) for insightful discussions and review of the manuscript, Sofia Rebelo and Silvia Cardoso for mouse breeding and genotyping, Pedro Almada and Nuno Pimpao Martins (IGC Imaging Facility) for technical support, Karen Berman de Ruiz and Joana Bom (IGC Animal Facility) for germ-free breeding, Joana Tavares, Rogerio Amino, and Robert Menard (Institute Pasteur) for technical support, Alekos Athanasiadis and Jocelyne Demengeot for insightful discussions, Pascal Gagneaux (University of California San Diego), and Daniel Mucida (Rockefeller University) for critical review of the initial version of the manuscript. Financial support from the Bill and Melinda Gates Foundation (OPP1024563), Fundacao para a Ciencia e Tecnologia (RECI-IMI-IMU-0038-2012), and European Research Council (ERC-2011-AdG 294709-DAMAGECONTROL) (to M.P.S.) and Fundacao para a Ciencia e a Tecnologia (SFRH/BD/51176/2010) within the PhDProgram of Integrative Biomedical Science of the Instituto Gulbenkian de Ciencia (to B.Y.) is gratefully acknowledged. The Division of Intramural Research, National Institute of Allergy and Infectious Diseases, and NIH supported the Mali cohort study. Mouse axenization was supported by the EMMA, EU FP7 Capacities Specific Program.