Gut microbiota elicits a protective immune response against malaria transmission

Bahtiyar Yilmaz, Silvia Portugal, Tuan  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

Research output: Contribution to journalArticle

114 Citations (Scopus)

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. PaperFlick

Original languageEnglish (US)
Pages (from-to)1277-1289
Number of pages13
JournalCell
Volume159
Issue number6
DOIs
StatePublished - Dec 4 2014
Externally publishedYes

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Malaria
Plasmodium
Anti-Idiotypic Antibodies
Galactosyltransferases
Antibodies
Escherichia coli
Uridine Diphosphate Galactose
Glycosylation
Galactosides
Cytotoxicity
Sporozoites
Anopheles
Genetic Selection
Polysaccharides
Skin
Infection
Culicidae
Genes
Vaccination
Gastrointestinal Microbiome

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Yilmaz, B., Portugal, S., Tran, T., Gozzelino, R., Ramos, S., Gomes, J., ... Soares, M. P. (2014). Gut microbiota elicits a protective immune response against malaria transmission. Cell, 159(6), 1277-1289. https://doi.org/10.1016/j.cell.2014.10.053

Gut microbiota elicits a protective immune response against malaria transmission. / Yilmaz, Bahtiyar; Portugal, Silvia; Tran, Tuan ; Gozzelino, Raffaella; Ramos, Susana; Gomes, Joana; Regalado, Ana; Cowan, Peter J.; D'Apice, Anthony J F; Chong, Anita S.; Doumbo, Ogobara K.; Traore, Boubacar; Crompton, Peter D.; Silveira, Henrique; Soares, Miguel P.

In: Cell, Vol. 159, No. 6, 04.12.2014, p. 1277-1289.

Research output: Contribution to journalArticle

Yilmaz, B, Portugal, S, Tran, T, Gozzelino, R, Ramos, S, Gomes, J, Regalado, A, Cowan, PJ, D'Apice, AJF, Chong, AS, Doumbo, OK, Traore, B, Crompton, PD, Silveira, H & Soares, MP 2014, 'Gut microbiota elicits a protective immune response against malaria transmission', Cell, vol. 159, no. 6, pp. 1277-1289. https://doi.org/10.1016/j.cell.2014.10.053
Yilmaz B, Portugal S, Tran T, Gozzelino R, Ramos S, Gomes J et al. Gut microbiota elicits a protective immune response against malaria transmission. Cell. 2014 Dec 4;159(6):1277-1289. https://doi.org/10.1016/j.cell.2014.10.053
Yilmaz, Bahtiyar ; Portugal, Silvia ; Tran, Tuan  ; Gozzelino, Raffaella ; Ramos, Susana ; Gomes, Joana ; Regalado, Ana ; Cowan, Peter J. ; D'Apice, Anthony J F ; Chong, Anita S. ; Doumbo, Ogobara K. ; Traore, Boubacar ; Crompton, Peter D. ; Silveira, Henrique ; Soares, Miguel P. / Gut microbiota elicits a protective immune response against malaria transmission. In: Cell. 2014 ; Vol. 159, No. 6. pp. 1277-1289.
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