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CAMPYLOBACTER JEJUNI DESTABILISES GUT HOMEOSTASIS BY INDUCING MYD88-INDEPENDENT INFLAMMATION
LM Friis1, M Keelan2, DE Taylor1
1Department of Medical Microbiology and Immunology, 2Department of Laboratory Medicine and Pathology, University of Alberta
Campylobacter infections are commonly associated with disruption of the intestinal epithelial cell barrier, yet the pathogenic and virulence mechanisms used by this bacterium to alter homeostasis in the gut remain unsolved. The cytokine interleukin-6 (IL-6) is important for maintenance of the intestinal epithelium and recognition of gut flora, yet is also pro-inflammatory and plays a critical role in governing the outcome of an innate immune response. This study provides a unique insight into the human immune signalling pathway initiated by Campylobacter infections in vitro, and investigates the bacterial antigens responsible for destabilisation of gastrointestinal equilibrium.
Cytokine secretion from Caco-2 intestinal epithelial cells was assessed in response to Campylobacter jejuni infections with particular focus on the acute phase response gene IL-6. IL-6 secretion, in response to infection with eight different C. jejuni isolates, was elevated between 2 and 12 fold compared to that induced by the commensal organism Lactobacillus rhamnosus GG. These data were supported by gene expression using real-time PCR and corresponded with phenotypic changes in polarised cell monolayers. Although host cell pattern recognition receptors have yet to be determined, siRNA knockdown experiments suggest this response is independent of myeloid differentiation factor 88 (MyD88) signalling. The host response to C. jejuni 81116 infection was investigated in greater detail by antibiotic treatment, sonication and cell fractionation methods. These methods identified a cell envelope localised antigen as mediating IL-6 induced inflammation.
We report on how Campylobacter colonisation of the gastrointestinal tract promotes inflammation and diarrhoeal disease through induction of MyD88-independent IL-6 signalling cascades. Further investigations into the specific bacterial and cellular signalling components associated with the IL-6 response will provide insight into the mechanism, by which, Campylobacter mediates gastrointestinal inflammatory disease.