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

Vesna Melkebeek (UGent) , K Rasschaert, Philippe Bellot (UGent) , K Tilleman, Herman Favoreel (UGent) , Dieter Deforce (UGent) , Bruno De Geest (UGent) , Bruno Goddeeris (UGent) and Eric Cox (UGent)
(2012) MUCOSAL IMMUNOLOGY. 5(6). p.635-645
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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.
Keywords
SUSCEPTIBILITY, VESICLES, IMMUNIZATION, CORONAVIRUS, MECHANISMS, DEPENDENT ENDOCYTOSIS, PORCINE, CHLAMYDIA-TRACHOMATIS, HUMAN EPITHELIAL-CELLS, ENTEROTOXIGENIC ESCHERICHIA-COLI

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MLA
Melkebeek, Vesna, et al. “Targeting Aminopeptidase N, a Newly Identified Receptor for F4ac Fimbriae, Enhances the Intestinal Mucosal Immune Response.” MUCOSAL IMMUNOLOGY, vol. 5, no. 6, 2012, pp. 635–45, doi:10.1038/mi.2012.37.
APA
Melkebeek, V., Rasschaert, K., Bellot, P., Tilleman, K., Favoreel, H., Deforce, D., … Cox, E. (2012). Targeting aminopeptidase N, a newly identified receptor for F4ac fimbriae, enhances the intestinal mucosal immune response. MUCOSAL IMMUNOLOGY, 5(6), 635–645. https://doi.org/10.1038/mi.2012.37
Chicago author-date
Melkebeek, Vesna, K Rasschaert, Philippe Bellot, K Tilleman, Herman Favoreel, Dieter Deforce, Bruno De Geest, Bruno Goddeeris, and Eric Cox. 2012. “Targeting Aminopeptidase N, a Newly Identified Receptor for F4ac Fimbriae, Enhances the Intestinal Mucosal Immune Response.” MUCOSAL IMMUNOLOGY 5 (6): 635–45. https://doi.org/10.1038/mi.2012.37.
Chicago author-date (all authors)
Melkebeek, Vesna, K Rasschaert, Philippe Bellot, K Tilleman, Herman Favoreel, Dieter Deforce, Bruno De Geest, Bruno Goddeeris, and Eric Cox. 2012. “Targeting Aminopeptidase N, a Newly Identified Receptor for F4ac Fimbriae, Enhances the Intestinal Mucosal Immune Response.” MUCOSAL IMMUNOLOGY 5 (6): 635–645. doi:10.1038/mi.2012.37.
Vancouver
1.
Melkebeek V, Rasschaert K, Bellot P, Tilleman K, Favoreel H, Deforce D, et al. Targeting aminopeptidase N, a newly identified receptor for F4ac fimbriae, enhances the intestinal mucosal immune response. MUCOSAL IMMUNOLOGY. 2012;5(6):635–45.
IEEE
[1]
V. Melkebeek et al., “Targeting aminopeptidase N, a newly identified receptor for F4ac fimbriae, enhances the intestinal mucosal immune response,” MUCOSAL IMMUNOLOGY, vol. 5, no. 6, pp. 635–645, 2012.
@article{3106838,
  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.}},
  author       = {{Melkebeek, Vesna and Rasschaert, K and Bellot, Philippe and Tilleman, K and Favoreel, Herman and Deforce, Dieter and De Geest, Bruno and Goddeeris, Bruno and Cox, Eric}},
  issn         = {{1933-0219}},
  journal      = {{MUCOSAL IMMUNOLOGY}},
  keywords     = {{SUSCEPTIBILITY,VESICLES,IMMUNIZATION,CORONAVIRUS,MECHANISMS,DEPENDENT ENDOCYTOSIS,PORCINE,CHLAMYDIA-TRACHOMATIS,HUMAN EPITHELIAL-CELLS,ENTEROTOXIGENIC ESCHERICHIA-COLI}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{635--645}},
  title        = {{Targeting aminopeptidase N, a newly identified receptor for F4ac fimbriae, enhances the intestinal mucosal immune response}},
  url          = {{http://doi.org/10.1038/mi.2012.37}},
  volume       = {{5}},
  year         = {{2012}},
}

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