TY - JOUR
T1 - Gut microbiota elicits a protective immune response against malaria transmission
AU - Yilmaz, Bahtiyar
AU - Portugal, Silvia
AU - Tran, Tuan M.
AU - Gozzelino, Raffaella
AU - Ramos, Susana
AU - Gomes, Joana
AU - Regalado, Ana
AU - Cowan, Peter J.
AU - D'Apice, Anthony J F
AU - Chong, Anita S.
AU - Doumbo, Ogobara K.
AU - Traore, Boubacar
AU - Crompton, Peter D.
AU - Silveira, Henrique
AU - Soares, Miguel P.
N1 - PMID:25480293
WOS:000346652900008
PY - 2014/12/4
Y1 - 2014/12/4
N2 - 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
AB - 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
UR - http://www.scopus.com/inward/record.url?scp=84920809160&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2014.10.053
DO - 10.1016/j.cell.2014.10.053
M3 - Article
C2 - 25480293
AN - SCOPUS:84920809160
SN - 0092-8674
VL - 159
SP - 1277
EP - 1289
JO - Cell
JF - Cell
IS - 6
ER -
