title: 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.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal.
authors.forename: Bahtiyar
authors.initials: B
authors.lastname: Yilmaz
authors.affiliation: Laboratory 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.
authors.forename: Silvia
authors.initials: S
authors.lastname: Portugal
authors.affiliation: Laboratory 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.
authors.forename: Tuan M
authors.initials: TM
authors.lastname: Tran
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Gozzelino
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal.
authors.forename: Susana
authors.initials: S
authors.lastname: Ramos
authors.affiliation: Instituto 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.
authors.forename: Joana
authors.initials: J
authors.lastname: Gomes
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Regalado
authors.affiliation: Immunology Research Centre, St. Vincent's Hospital, Fitzroy, Melbourne, VIC 3065, Australia; Department of Medicine, University of Melbourne, Parkville, VIC 2900, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Cowan
authors.affiliation: Immunology Research Centre, St. Vincent's Hospital, Fitzroy, Melbourne, VIC 3065, Australia; Department of Medicine, University of Melbourne, Parkville, VIC 2900, Australia.
authors.forename: Anthony J F
authors.initials: AJ
authors.lastname: d'Apice
authors.affiliation: Section of Transplantation, Department of Surgery, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA.
authors.forename: Anita S
authors.initials: AS
authors.lastname: Chong
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, 1805 Bamako, Mali.
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
authors.affiliation: Mali International Center of Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, 1805 Bamako, Mali.
authors.forename: Boubacar
authors.initials: B
authors.lastname: Traore
authors.affiliation: Laboratory 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.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Crompton
authors.affiliation: 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.
authors.forename: Henrique
authors.initials: H
authors.lastname: Silveira
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156 Oeiras, Portugal. Electronic address: mpsoares@igc.gulbenkian.pt.
authors.forename: Miguel P
authors.initials: MP
authors.lastname: Soares
mesh_terms: D000328:Adult; D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D045744:Cell Line, Tumor; D002648:Child; D004926:Escherichia coli / Q000145:classification / Q000276:immunology / Q000502:physiology*; D005260:Female; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000382:microbiology; D005856:Germ-Free Life; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology / Q000635:transmission*; D051379:Mice; D010961:Plasmodium / Q000145:classification / Q000254:growth & development / Q000276:immunology / Q000502:physiology*; D010963:Plasmodium falciparum / Q000276:immunology / Q000502:physiology; D011134:Polysaccharides / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000819:agonists
chemical_list: D000907:Antibodies, Bacterial; D000913:Antibodies, Protozoan; D001324:Autoantigens; D007075:Immunoglobulin M; D011134:Polysaccharides; D051217:Toll-Like Receptor 9; D005700:Galactosyltransferases