Pseudaminic acid on Campylobacter jejuni flagella modulates dendritic cell IL-10 expression via Siglec-10 receptor: a novel flagellin-host interaction

Holly N. Stephenson, Dominic C. Mills, Hannah Jones, Enea Milioris, Alastair Copland, Nick Dorrell, Brendan W. Wren, Paul R. Crocker, David Escors, Mona Bajaj-Elliott (Lead / Corresponding author)

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    39 Citations (Scopus)
    161 Downloads (Pure)

    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 interleukin 10 (IL-10) in vitro, a cellular event that was MyD88- and p38 MAPK-signalling dependent. Utilizing 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 overexpressing 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 Salmonella Typhimurium flagella-TLR5 driven pro-inflammatory axis, C. jejuni flagella instead promote an anti-inflammatory axis via glycan-Siglec-10 engagement.

    Original languageEnglish
    Pages (from-to)1487-1498
    Number of pages12
    JournalJournal of Infectious Diseases
    Volume210
    Issue number9
    DOIs
    Publication statusPublished - 1 Nov 2014

    Keywords

    • Animals
    • Campylobacter Infections
    • Campylobacter jejuni
    • Dendritic Cells
    • Flagella
    • Host-Pathogen Interactions
    • Humans
    • Interleukin-10
    • Lectins
    • Mice, Inbred C57BL
    • Receptors, Cell Surface
    • Sugar Acids

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