BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Talks.cam//talks.cam.ac.uk//
X-WR-CALNAME:Talks.cam
BEGIN:VEVENT
SUMMARY:Gut Microbiota Confers Protection Against Malaria - Miguel Soares\
 , Instituto Gulbenkian de Ciência\, Portugal
DTSTART:20150501T120000Z
DTEND:20150501T130000Z
UID:TALK57580@talks.cam.ac.uk
CONTACT:Dr Tennie Videler
DESCRIPTION:As for other self-antigens\, self-glycans cannot be targeted b
 y the immune system when also expressed by pathogens. However\, this can b
 e overcome via natural selection of loss-of-function mutations in genes re
 gulating the expression of self-glycans. This phenomenon is well illustrat
 ed for the natural selection of loss-of-function mutations in the human UD
 P-Galactose:β-galactoside-α1-3-galactosyltransferase (α1\,3GT) gene\, w
 hich in other mammals encodes an enzyme producing the Galα1-3Galβ1-4GlcN
 Ac-R (α-gal) glycan. Given that components of the human gut microbiota ca
 n express the α-gal glycan\, we reasoned that anti-α-gal antibodies gene
 rated against these microbiota components might confer protection against 
 pathogens expressing -gal. We found that this is the case for the human
  gut pathobiont E. coli O86:B7\, which induces the production of anti-α g
 al antibodies that confer protection against Plasmodium infection\, the ca
 usative agent of malaria. This notion is supported by several independent 
 observations: i) Both Plasmodium spp. and E. coli O86:B7 express the α-ga
 l glycan\, ii) when colonized by E. coli O86:B7\, α1\,3GT deficient mice\
 , which like humans can produce anti-α-gal antibodies\, are protected aga
 inst malaria and iii) anti-α-gal antibodies are associated with protectio
 n against malaria in humans. The mechanism underlying the protective effec
 t exerted by anti--gal antibodies is mediated via Plasmodium sporozoite
  targeting for complement-mediated cytotoxicity\, immediately after inocul
 ation in the skin by Anopheles mosquitoes. This cytotoxic effect prevents 
 sporozoites from reaching the liver\, thus avoiding the establishment of i
 nfection. Vaccination against synthetic α-gal confers sterile protection 
 against malaria in α1\,3GT deficient mice\, suggesting that a similar app
 roach may be used in humans. \n
LOCATION:MPLT\, MRC-LMB\, Francis Crick Avenue\, Cambridge Biomedical Camp
 us\, CB2 0QH
END:VEVENT
END:VCALENDAR