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Title: Innate immune recognition of glycosylated surface determinants of Campylobacter jejuni
Author: Stephenson, H. N.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2012
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Campylobacter jejuni, a commensal in poultry members, causes acute gastroenteritis in humans. Understanding of Campylobacter jejuni pathogenesis lags far behind that of other gastrointestinal pathogens despite Campylobacter sp. being a leading cause of bacterial gastroenteritis in the developed world. In this study C. jejuni was shown to induce high levels of IL-10 from dendritic cells, a potent anti-inflammatory cytokine. IL-10 secretion was induced by the flagella of C. jejuni, a protein based filament structure that is modified by sialic-acid like structures. These sugar structures were shown to be critical in the induction of IL-10. C. jejuni lacking flagella induced lower levels of p38 activation, and inhibition of p38 reduced IL-10 secretion. Interestingly Myd88-dependant TLR signalling was shown to be critical for the induction of IL-10 despite the inability of C. jejuni flagellin to activate TLR5. We showed that C. jejuni can bind to Siglec-10, an interaction that was dependent on the glycosylation of the flagella. We speculate that the addition of glycan structures to C. jejuni flagellin proteins may be a host-subversion strategy via the induction of IL-10. C. jejuni strains isolated from infected humans can be sub-divided into two distinct phylogenetic clades. We sought to investigate whether the lipooligosaccharide (LOS) structure is distinct between the two clades. The structures of the LOS from 15 different strains were analysed. Variation in the oligosaccharide (OS) structure, amide linkages connecting the acyl chains to the lipid A backbone, and phosphorylation of the lipid A between the strains were observed. Phosphorylation of the lipid A and sialylation of the OS correlated with the induction of TNF-α from monocytes. Interestingly, the sialylation of the OS correlated with the phylogenetic clade. Collectively the data presented highlights the importance of glycosylated surface determinants on pathogenic bacteria to manipulate the host innate immune response.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available