Targeting aminopeptidase N, a newly identified receptor for F4ac fimbriae, enhances the intestinal mucosal immune response.
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.
Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. Vesna.Melkebeek@ugent.be
V
V
Melkebeek
K
K
Rasschaert
P
P
Bellot
K
K
Tilleman
H
H
Favoreel
D
D
Deforce
B G
BG
De Geest
B M
BM
Goddeeris
E
E
Cox
D000818:Animals; D001422:Bacterial Adhesion; D018826:CD13 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism; D003967:Diarrhea / Q000276:immunology / Q000382:microbiology; D004705:Endocytosis / Q000276:immunology; D020895:Enterocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D054307:Enterotoxigenic Escherichia coli / Q000737:chemistry / Q000378:metabolism* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology; D010861:Fimbriae, Bacterial / Q000378:metabolism*; D018928:Immunity, Mucosal; D007136:Immunoglobulins / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008871:Microvilli / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D011485:Protein Binding; D040901:Proteomics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013552:Swine; D014162:Transfection
D002966:Clathrin; D007136:Immunoglobulins; D011956:Receptors, Cell Surface; D018826:CD13 Antigens