TITLE

Targeting aminopeptidase N, a newly identified receptor for F4ac fimbriae, enhances the intestinal mucosal immune response

AUTHOR(S)
Melkebeek, V; Rasschaert, K; Bellot, P; Tilleman, K; Favoreel, H; Deforce, D; De Geest, B G; Goddeeris, B M; Cox, E
PUB. DATE
November 2012
SOURCE
Mucosal Immunology (1933-0219);Nov2012, Vol. 5 Issue 6, p635
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Enterotoxigenic Escherichia coli (ETEC) are a major cause of diarrhea in human and animal. In piglets, ETEC having F4 fimbriae (F4+ ETEC) induce severe diarrhea, dependent on the presence of receptors for F4 (F4R). In this study, porcine aminopeptidase N (pAPN) was identified as an F4R by comparative proteomic analysis of brush border proteins of F4R+ and F4R− pigs and by adherence/internalization experiments on pAPN-transfected cells. Binding of F4 fimbriae to pAPN depended on sialic acid containing carbohydrate moieties, and resulted in clathrin-mediated endocytosis of the fimbriae. Endocytosis via pAPN was not restricted to F4 fimbriae, but was also observed for anti-pAPN antibodies. Both F4 fimbriae- and pAPN-specific antibodies were taken up in vivo by porcine enterocytes and induced subsequently a rapid immunoglobulin A and G response. In conclusion, we identified pAPN as an endocytotic receptor for F4 fimbriae and highlight the opportunity to target vaccine antigens to this epithelial receptor.
ACCESSION #
82724269

 

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