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

Melkebeek, V; Rasschaert, K; Bellot, P; Tilleman, K; Favoreel, H; Deforce, D; De Geest, B G; Goddeeris, B M; Cox, E
November 2012
Mucosal Immunology (1933-0219);Nov2012, Vol. 5 Issue 6, p635
Academic Journal
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.


Related Articles

  • Variation in 12 porcine genes involved in the carbohydrate moiety assembly of glycosphingolipids does not account for differential binding of F4 Escherichia coli and their fimbriae. Goetstouwers, Tiphanie; Van Poucke, Mario; Coddens, Annelies; Nguyen, Van Ut; Melkebeek, Vesna; Deforce, Dieter; Cox, Eric; Peelman, Luc J. // BMC Genetics;2014, Vol. 15 Issue 1, p1 

    Background Glycosphingolipids (GSLs) are important membrane components composed of a carbohydrate structure attached to a hydrophobic ceramide. They can serve as specific membrane receptors for microbes and microbial products, such as F4 Escherichia coli (F4 ETEC) and isolated F4 fimbriae. The...

  • Development of A Loop-Mediated Isothermal Amplification (LAMP) for the Detection of F5 Fimbriae Gene in Enterotoxigenic Escherichia coli (ETEC). Jiang, Kuiyu; Zhu, Ying; Liu, Wenxin; Feng, Yufei; He, Lili; Guan, Weikun; Hu, Wenxia; Shi, Dongfang // Current Microbiology;Nov2012, Vol. 65 Issue 5, p633 

    The objective of this study was to establish a loop-mediated isothermal amplification (LAMP) method for the detection of F5 fimbriae gene in Enterotoxigenic Escherichia coli. A set of four primers were designed based on the conservative sequence of coding F5 fimbriae. Temperature and time...

  • Proteomic Analysis of Duodenal Tissue from Escherichia coli F18-Resistant and -Susceptible Weaned Piglets. Wu, Zhengchang; Xia, Riwei; Yin, Xuemei; Huo, Yongjiu; Zhu, Guoqiang; Wu, Shenglong; Bao, Wenbin // PLoS ONE;Jun2015, Vol. 10 Issue 6, p1 

    Diarrhea and edema disease in weaned piglets due to infection by Escherichia coli F18 is a leading cause of economic loss in the pig industry. Resistance to E. coli F18 depends on expression of receptors on intestinal epithelial cells, and individual immunity. This study was conducted in Sutai...

  • Escherichia coli Hfq has distinct interaction surfaces for DsrA, rpoS and poly(A) RNAs. Mikulecky, Peter J.; Kaw, Meenakshi K.; Brescia, Cristin C.; Takach, Jennifer C.; Sledjeski, Darren D.; Feig, Andrew L. // Nature Structural & Molecular Biology;Dec2004, Vol. 11 Issue 12, p1206 

    The bacterial Sm-like protein Hfq facilitates RNA-RNA interactions involved in post-transcriptional regulation of the stress response. Specifically, Hfq helps pair noncoding RNAs (ncRNAs) with complementary regions of target mRNAs. To probe the mechanism of this pairing, we generated a series of...

  • Proteomic Profiling of Escherichia Coli in Response to Heavy Metals Stress. Isarankura-Na-Ayudhya, Patcharee; Isarankura-Na-Ayudhya, Chartchalerm; Treeratanapaiboon, Lertyot; Kasikun, Kulanan; Thipkeaw, Kreangkrai; Prachayasittikul, Virapong // European Journal of Scientific Research;Jan2009, Vol. 25 Issue 4, p679 

    Over utilization of natural resources and growing trend of industrialization raise a global concern on environmental toxic metals to living organisms. Using two-dimensional gel electrophoresis (2-DE) in combination with peptide mass fingerprinting, significant changes of differentially expressed...

  • A new method for the construction of translationally coupled operons in a bacterial chromosome. Gulevich, A. Yu.; Skorokhodova, A. Yu.; Ermishev, V. Yu.; Krylov, A. A.; Minaeva, N. I.; Polonskaya, Z. M.; Zimenkov, D. V.; Biryukova, I. V.; Mashko, S. V. // Molecular Biology;Jun2009, Vol. 43 Issue 3, p505 

    A new method for the construction of translationally coupled operons in a bacterial chromosome was developed on the basis of the recombineering approach. The method includes the in vitro construction of an artificial operon with an efficiently translated proximal cistron, its insertion into the...

  • Absolute protein expression profiling estimates the relative contributions of transcriptional and translational regulation. Lu, Peng; Vogel, Christine; Wang, Rong; Yao, Xin; Marcotte, Edward M. // Nature Biotechnology;Jan2007, Vol. 25 Issue 1, p117 

    We report a method for large-scale absolute protein expression measurements (APEX) and apply it to estimate the relative contributions of transcriptional- and translational-level gene regulation in the yeast and Escherichia coli proteomes. APEX relies upon correcting each protein's mass...

  • Optimality and evolutionary tuning of the expression level of a protein. Dekel, Erez; Alon, Uri // Nature;7/28/2005, Vol. 436 Issue 7050, p588 

    Different proteins have different expression levels. It is unclear to what extent these expression levels are optimized to their environment. Evolutionary theories suggest that protein expression levels maximize fitness, but the fitness as a function of protein level has seldom been directly...

  • Accurate and Efficient Resolution of Overlapping Isotopic Envelopes in Protein Tandem Mass Spectra. Kaijie Xiao; Fan Yu; Houqin Fang; Bingbing Xue; Yan Liu; Zhixin Tian // Scientific Reports;10/9/2015, p1 

    It has long been an analytical challenge to accurately and efficiently resolve extremely dense overlapping isotopic envelopes (OIEs) in protein tandem mass spectra to confidently identify proteins. Here, we report a computationally efficient method, called OIE_CARE, to resolve OIEs by...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics