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Delineation of the Innate and Adaptive T-Cell Immune Outcome in the Human Host in Response to Campylobacter jejuni Infection

Edwards, LA; Nistala, K; Mills, DC; Stephenson, HN; Zilbauer, M; Wren, BW; Dorrell, N; ... Bajaj-Elliott, M; + view all (2010) Delineation of the Innate and Adaptive T-Cell Immune Outcome in the Human Host in Response to Campylobacter jejuni Infection. PLOS ONE , 5 (11) , Article e15398. 10.1371/journal.pone.0015398. Green open access

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Abstract

Background: Campylobacter jejuni is the most prevalent cause of bacterial gastroenteritis worldwide. Despite the significant health burden this infection presents, molecular understanding of C. jejuni-mediated disease pathogenesis remains poorly defined. Here, we report the characterisation of the early, innate immune response to C. jejuni using an ex-vivo human gut model of infection. Secondly, impact of bacterial-driven dendritic cell activation on T-cell mediated immunity was also sought.Methodology: Healthy, control paediatric terminal ileum or colonic biopsy tissue was infected with C. jejuni for 8-12 hours. Bacterial colonisation was followed by confocal microscopy and mucosal innate immune responses measured by ELISA. Marked induction of IFN gamma with modest increase in IL-22 and IL-17A was noted. Increased mucosal IL-12, IL-23, IL-1 beta and IL-6 were indicative of a cytokine milieu that may modulate subsequent T-cell mediated immunity. C. jejuni-driven human monocyte-derived dendritic cell activation was followed by analyses of T cell immune responses utilising flow cytometry and ELISA. Significant increase in Th-17, Th-1 and Th-17/Th-1 double-positive cells and corresponding cytokines was observed. The ability of IFN gamma, IL-22 and IL-17 cytokines to exert host defence via modulation of C. jejuni adhesion and invasion to intestinal epithelia was measured by standard gentamicin protection assay.Conclusions: Both innate and adaptive T cell-immunity to C. jejuni infection led to the release of IFN gamma, IL-22 and IL-17A; suggesting a critical role for this cytokine triad in establishing host anti-microbial immunity during the acute and effectors phase of infection. In addition, to their known anti-microbial functions; IL-17A and IL-17F reduced the number of intracellular C. jejuni in intestinal epithelia, highlighting a novel aspect of how IL-17 family members may contribute to protective immunity against C. jejuni.

Type: Article
Title: Delineation of the Innate and Adaptive T-Cell Immune Outcome in the Human Host in Response to Campylobacter jejuni Infection
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0015398
Publisher version: http://dx.doi.org/10.1371/journal.pone.0015398
Language: English
Additional information: © 2010 Edwards et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This study was supported by the Institute of Child Health/Great Ormond Street Hospital Special Trustees 05ID04 (to MB-E and KJL). KN is an Arthritis Research Campaign Clinical Fellow (ref 17998). The following were supported by PhD studentships: DCM (Bloomsbury Colleges), HNS (Biomedical Research Centre) and MZ (MRC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: INFLAMMATORY-BOWEL-DISEASE, NATURAL-KILLER-CELLS, DENDRITIC CELLS, CYTOKINE PRODUCTION, INTESTINAL-MUCOSA, ESCHERICHIA-COLI, INTERLEUKIN 22, IN-VITRO, PATHOGENESIS, BETA-DEFENSIN-2
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/374831
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