Targeting aminopeptidase N, a newly identified receptor for F4ac fimbriae, enhances the intestinal mucosal immune response
- Author
- 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)
- Organization
- 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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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-3106838
- 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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