Delineation of the innate and adaptive T-cell immune outcome in the human host in response to Campylobacter jejuni infection.
<h4>Background</h4>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 charac...
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2010
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oai:doaj.org-article:4c162ee640d244f0abc9b10af7c40bfd2021-11-18T07:37:02ZDelineation of the innate and adaptive T-cell immune outcome in the human host in response to Campylobacter jejuni infection.1932-620310.1371/journal.pone.0015398https://doaj.org/article/4c162ee640d244f0abc9b10af7c40bfd2010-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21085698/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology</h4>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 IFNγ with modest increase in IL-22 and IL-17A was noted. Increased mucosal IL-12, IL-23, IL-1β 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 IFNγ, 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.<h4>Conclusions</h4>Both innate and adaptive T cell-immunity to C. jejuni infection led to the release of IFNγ, 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.Lindsey A EdwardsKiran NistalaDominic C MillsHolly N StephensonMatthias ZilbauerBrendan W WrenNick DorrellKeith J LindleyLucy R WedderburnMona Bajaj-ElliottPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 11, p e15398 (2010) |
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Medicine R Science Q Lindsey A Edwards Kiran Nistala Dominic C Mills Holly N Stephenson Matthias Zilbauer Brendan W Wren Nick Dorrell Keith J Lindley Lucy R Wedderburn Mona Bajaj-Elliott Delineation of the innate and adaptive T-cell immune outcome in the human host in response to Campylobacter jejuni infection. |
| description |
<h4>Background</h4>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.<h4>Methodology</h4>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 IFNγ with modest increase in IL-22 and IL-17A was noted. Increased mucosal IL-12, IL-23, IL-1β 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 IFNγ, 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.<h4>Conclusions</h4>Both innate and adaptive T cell-immunity to C. jejuni infection led to the release of IFNγ, 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. |
| format |
article |
| author |
Lindsey A Edwards Kiran Nistala Dominic C Mills Holly N Stephenson Matthias Zilbauer Brendan W Wren Nick Dorrell Keith J Lindley Lucy R Wedderburn Mona Bajaj-Elliott |
| author_facet |
Lindsey A Edwards Kiran Nistala Dominic C Mills Holly N Stephenson Matthias Zilbauer Brendan W Wren Nick Dorrell Keith J Lindley Lucy R Wedderburn Mona Bajaj-Elliott |
| author_sort |
Lindsey A Edwards |
| title |
Delineation of the innate and adaptive T-cell immune outcome in the human host in response to Campylobacter jejuni infection. |
| title_short |
Delineation of the innate and adaptive T-cell immune outcome in the human host in response to Campylobacter jejuni infection. |
| title_full |
Delineation of the innate and adaptive T-cell immune outcome in the human host in response to Campylobacter jejuni infection. |
| title_fullStr |
Delineation of the innate and adaptive T-cell immune outcome in the human host in response to Campylobacter jejuni infection. |
| title_full_unstemmed |
Delineation of the innate and adaptive T-cell immune outcome in the human host in response to Campylobacter jejuni infection. |
| title_sort |
delineation of the innate and adaptive t-cell immune outcome in the human host in response to campylobacter jejuni infection. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2010 |
| url |
https://doaj.org/article/4c162ee640d244f0abc9b10af7c40bfd |
| work_keys_str_mv |
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| _version_ |
1718423157544583168 |