Abstract
BackgroundAlthough 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.Methodology/Principal FindingsGnotobiotic 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.Conclusion/SignificanceWe 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.
Highlights
Campylobacter jejuni is the most important cause of bacterial diarrhea in developing as well as in industrialized countries
Survey of clinical conditions revealed that irrespectively whether mice had been infected with the C. jejuni parental strain NCTC11168, the mutant strain NCTC11168::cj0268c or its complemented version NCTC11168::cj0268c-comp-cj0268c, similar intestinal colonization densities were accompanied by comparable disease symptoms of enterocolitis as indicated by similar clinical scores over time (Fig. 3)
Gnotobiotic IL-102/2 mice infected with the C. jejuni mutant strain NCTC11168::cj0268c displayed longer small intestines and colons as compared to mice infected with the parental strain NCTC11168 (p,0.05) or complemented strain NCTC11168::cj0268c-comp-cj0268c (p,0.05 and p,0.01, respectively; Fig. 4AB) indicative for significantly less distinct intestinal pathology
Summary
Campylobacter jejuni is the most important cause of bacterial diarrhea in developing as well as in industrialized countries. A successful infection with C. jejuni requires adherence of the pathogen to host cells and several proteins of C. jejuni that contribute to this initial interaction have been characterized in the past. PEB1 as an element of an ABC transporter and CapA, representing an autotransporter protein, mediate adherence and are important for C. jejuni colonization of mice and chicken, respectively [8,9]. 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. The immunopathological impact of this gene, has not been investigated in vivo so far
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
