Abstract
We have recently shown that, within 1 week following peroral Campylobacter jejuni infection, conventional infant mice develop self-limiting enteritis. We here investigated the role of IL-23, IL-22, and IL-18 during C. jejuni strain 81-176 infection of infant mice. The pathogen efficiently colonized the intestines of IL-18(-/-) mice only, but did not translocate to extra-intestinal compartments. At day 13 postinfection (p.i.), IL-22(-/-) mice displayed lower colonic epithelial apoptotic cell numbers as compared to wildtype mice, whereas, conversely, colonic proliferating cells increased in infected IL-22(-/-) and IL-18(-/-) mice. At day 6 p.i., increases in neutrophils, T and B lymphocytes were less pronounced in gene-deficient mice, whereas regulatory T cell numbers were lower in IL-23p19(-/-) and IL-22(-/-) as compared to wildtype mice, which was accompanied by increased colonic IL-10 levels in the latter. Until then, colonic pro-inflammatory cytokines including TNF, IFN-γ, IL-6, and MCP-1 increased in IL-23p19(-/-) mice, whereas IL-18(-/-) mice exhibited decreased cytokine levels and lower colonic numbers of T and B cell as well as of neutrophils, macrophages, and monocytes as compared to wildtype controls. In conclusion, IL-23, IL-22, and IL-18 are differentially involved in mediating C. jejuni-induced immunopathology of conventional infant mice.