title: Impact of Campylobacter jejuni cj0268c knockout mutation on intestinal colonization, translocation, and induction of immunopathology in gnotobiotic IL-10 deficient mice.
abstract: BACKGROUND
  Although Campylobacter jejuni infections have a high prevalence worldwide and represent a significant socioeconomic burden, the underlying molecular mechanisms of induced intestinal immunopathology are still not well understood. We have recently generated a C. jejuni mutant strain NCTC11168::cj0268c, which has been shown to be involved in cellular adhesion and invasion. The immunopathological impact of this gene, however, has not been investigated in vivo so far.
  
  
  RESULTS
  Gnotobiotic IL-10 deficient mice were generated by quintuple antibiotic treatment and perorally infected with C. jejuni mutant strain NCTC11168::cj0268c, its complemented version (NCTC11168::cj0268c-comp-cj0268c), or the parental strain NCTC11168. Kinetic analyses of fecal pathogen loads until day 6 post infection (p.i.) revealed that knockout of cj0268c did not compromise intestinal C. jejuni colonization capacities. Whereas animals irrespective of the analysed C. jejuni strain developed similar clinical symptoms of campylobacteriosis (i.e. enteritis), mice infected with the NCTC11168::cj0268c mutant strain displayed significant longer small as well as large intestinal lengths indicative for less distinct C. jejuni induced pathology when compared to infected control groups at day 6 p.i. This was further supported by significantly lower apoptotic and T cell numbers in the colonic mucosa and lamina propria, which were paralleled by lower intestinal IFN-γ and IL-6 concentrations at day 6 following knockout mutant NCTC11168::cj0268c as compared to parental strain infection. Remarkably, less intestinal immunopathology was accompanied by lower IFN-γ secretion in ex vivo biopsies taken from mesenteric lymphnodes of NCTC11168::cj0268c infected mice versus controls.
  
  
  CONCLUSIONS
  We here for the first time show that the cj0268c gene is involved in mediating C. jejuni induced immunopathogenesis in vivo. Future studies will provide further deep insights into the immunological and molecular interplays between C. jejuni and innate immunity in human campylobacteriosis.
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
authors.affiliation: Department of Medical Microbiology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Raimond
authors.initials: R
authors.lastname: Lugert
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Alutis
authors.affiliation: Department of Pathology/Research Center ImmunoSciences (RCIS), Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.affiliation: Department of Medical Microbiology, University Medical Center Göttingen, Göttingen, Germany ; Department of Clinical Chemistry/UMG-Laboratory, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Zautner
authors.affiliation: Department of Medical Microbiology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: A Malik
authors.initials: AM
authors.lastname: Tareen
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Ulf B
authors.initials: UB
authors.lastname: Göbel
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin, Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D018988:Bacterial Translocation / Q000235:genetics*; D016123:Campylobacter jejuni / Q000235:genetics / Q000502:physiology*; D005260:Female; D055786:Gene Knockout Techniques; D005856:Germ-Free Life; D006801:Humans; D016753:Interleukin-10 / Q000172:deficiency*; D007422:Intestines / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation
chemical_list: D001426:Bacterial Proteins; D016753:Interleukin-10