Sialylation of campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice

Huizinga, R. et al. (2012) Sialylation of campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice. PLoS ONE, 7(3), e34416. (doi:10.1371/journal.pone.0034416) (PMID:22470569) (PMCID:PMC3314637)

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Abstract

Background: Guillain-Barré syndrome (GBS) is a post-infectious polyradiculoneuropathy, frequently associated with antecedent Campylobacter jejuni (C. jejuni) infection. The presence of sialic acid on C. jejuni lipo-oligosaccharide (LOS) is considered a risk factor for development of GBS as it crucially determines the structural homology between LOS and gangliosides, explaining the induction of cross-reactive neurotoxic antibodies. Sialylated C. jejuni are recognised by TLR4 and sialoadhesin; however, the functional implications of these interactions in vivo are unknown.

Methodology/Principal Findings: In this study we investigated the effects of bacterial sialylation on phagocytosis and cytokine secretion by mouse myeloid cells in vitro and in vivo. Using fluorescently labelled GM1a/GD1a ganglioside-mimicking C. jejuni strains and corresponding (Cst-II-mutant) control strains lacking sialic acid, we show that sialylated C. jejuni was more efficiently phagocytosed in vitro by BM-MΦ, but not by BM-DC. In addition, LOS sialylation increased the production of IL-10, IL-6 and IFN-β by both BM-MΦ and BM-DC. Subsequent in vivo experiments revealed that sialylation augmented the deposition of fluorescent bacteria in splenic DC, but not macrophages. In addition, sialylation significantly amplified the production of type I interferons, which was independent of pDC.

Conclusions/Significance: These results identify novel immune stimulatory effects of C. jejuni sialylation, which may be important in inducing cross-reactive humoral responses that cause GBS

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Easton, Dr Alistair and Willison, Professor Hugh and Goodyear, Professor Carl and Donachie, Ms Anne Marie
Authors: Huizinga, R., Easton, A. S., Donachie, A. M., Guthrie, J., van Rijs, W., Heikema, A., Boon, L., Samsom, J. N., Jacobs, B. C., Willison, H. J., and Goodyear, C. S.
Subjects:Q Science > QH Natural history > QH301 Biology
R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Published Online:28 March 2012
Copyright Holders:Copyright © 2012 The Authors
First Published:First published in PLoS ONE 7(3):e34416
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
443301RA-associated factors and their affect on B cell targeted cell deathCarl GoodyearArthritis Research UK (ARC)MP/17653III -IMMUNOLOGY