Background Human Campylobacter jejuni infections are progressively rising
worldwide. Information about the molecular mechanisms underlying
campylobacteriosis, however, are limited. In the present study we investigated
whether cytokines such as IL-23, IL-22 and IL-18, which share pivotal
functions in host immunity, were involved in mediating intestinal and systemic
immunopathological responses upon C. jejuni infection. Methodology/Principal
Findings To assure stable infection, gnotobiotic (i.e. secondary abiotic) IL-
23p19-/-, IL-22-/- and IL-18-/- mice were generated by broad-spectrum
antibiotic treatment. Following peroral C. jejuni strain 81–176 infection,
mice of all genotypes harbored comparably high pathogenic loads in their
intestines. As compared to wildtype controls, however, IL-18-/- mice displayed
less distinct C. jejuni induced sequelae as indicated by less pronounced large
intestinal shrinkage and lower numbers of apoptotic cells in the colonic
epithelial layer at day 8 postinfection (p.i.). Furthermore, lower colonic
numbers of adaptive immune cells including regulatory T cells and B
lymphocytes were accompanied by less distinct secretion of pro-inflammatory
cytokines such as TNF and IFN-γ and lower IL-17A mRNA expression levels in
colonic ex vivo biopsies of infected IL-18-/- as compared to wildtype mice.
Upon C. jejuni infection, colonic IL-23p19 expression was up-regulated in
IL-18-/- mice only, whereas IL-22 mRNA levels were lower in uninfected and
infected IL-23p19-/- as well as infected IL-18-/- as compared to respective
wildtype control mice. Remarkably, not only intestinal, but also systemic
infection-induced immune responses were less pronounced in IL-18-/- mice as
indicated by lower TNF, IFN-γ and IL-6 serum levels as compared to wildtype
mice. Conclusion/Significance We here show for the first time that IL-18 is
essentially involved in mediating C. jejuni infection in the gnotobiotic mouse
model. Future studies need to further unravel the underlying regulatory
mechanisms orchestrating pathogen-host interaction