title: Delineation of the innate and adaptive T-cell immune outcome in the human host in response to Campylobacter jejuni infection.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Infectious Diseases and Microbiology, Institute of Child Health, London, United Kingdom.
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Edwards
authors.forename: Kiran
authors.initials: K
authors.lastname: Nistala
authors.forename: Dominic C
authors.initials: DC
authors.lastname: Mills
authors.forename: Holly N
authors.initials: HN
authors.lastname: Stephenson
authors.forename: Matthias
authors.initials: M
authors.lastname: Zilbauer
authors.forename: Brendan W
authors.initials: BW
authors.lastname: Wren
authors.forename: Nick
authors.initials: N
authors.lastname: Dorrell
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Lindley
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Wedderburn
authors.forename: Mona
authors.initials: M
authors.lastname: Bajaj-Elliott
mesh_terms: D056704:Adaptive Immunity; D002169:Campylobacter Infections / Q000276:immunology / Q000382:microbiology; D016123:Campylobacter jejuni / Q000276:immunology* / Q000502:physiology; D002648:Child; D016207:Cytokines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007421:Intestine, Small / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008297:Male; D009924:Organ Culture Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D016207:Cytokines; D007371:Interferon-gamma; D020381:Interleukin-17; D007378:Interleukins; D000097043:Interleukin-22