Pseudaminic Acid on Campylobacter jejuni Flagella Modulates Dendritic Cell IL-10 Expression via Siglec-10 Receptor: a Novel Flagellin-Host Interaction.


Stephenson, HN; Mills, DC; Jones, H; Milioris, E; Copland, A; Dorrell, N; Wren, BW; Crocker, PR; Escors, D; Bajaj-Elliott, M; (2014) Pseudaminic Acid on Campylobacter jejuni Flagella Modulates Dendritic Cell IL-10 Expression via Siglec-10 Receptor: a Novel Flagellin-Host Interaction. The Journal of infectious diseases. ISSN 0022-1899 DOI: 10.1093/infdis/jiu287

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Abstract

INTRODUCTION  Campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide. At present the identity of host-pathogen interactions that promote successful bacterial colonisation remain ill defined. Herein, we aimed to investigate C. jejuni-mediated effects on dendritic cell (DC) immunity. RESULTS  We found C. jejuni to be a potent inducer of human and murine DC IL-10 in vitro, a cellular event that was MyD88- and p38 MAPK-signalling dependent. Utilising a series of C. jejuni isogenic mutants we found the major flagellin protein, FlaA, modulated IL-10 expression, an intriguing observation as C. jejuni FlaA is not a TLR5 agonist. Further analysis revealed pseudaminic acid residues on the flagella contributed to DC IL-10 expression. We identified the ability of both viable C. jejuni and purified flagellum to bind to Siglec-10, an immune-modulatory receptor. In vitro infection of Siglec-10 over-expressing cells resulted in increased IL-10 expression in a p38-dependent manner. Detection of Siglec-10 on intestinal CD11c+ CD103+ DCs added further credence to the notion that this novel interaction may contribute to immune outcome during human infection. CONCLUSIONS  We propose that unlike the S. Typhimurium flagella-TLR5 driven pro-inflammatory axis, C. jejuni flagella instead promote an anti-inflammatory axis via glycan-Siglec-10 engagement.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Pathogen Molecular Biology
PubMed ID: 24823621
Web of Science ID: 344610600018
URI: http://researchonline.lshtm.ac.uk/id/eprint/1726156

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