Campylobacter jejuni induces extra-intestinal immuneresponses via Toll-like-receptor-4 signaling in conventional IL-10 deficientmice with chronic colitis

摘要

Campylobacter jejuni is one of the predominant causes for foodborne bacterial infections worldwide. We investigated whether signaling of C. jejuni-lipoproteins and -lipooligosaccharide via Toll-like-receptor (TLR) -2 and -4, respectively, is inducing intestinal and extra-intestinal immune responses following infection of conventional IL-10^−/− mice with chronic colitis. At day 3 following oral infection, IL-10^−/− mice lacking TLR-2 or TLR-4 harbored comparable C. jejuni strain ATCC 43431 loads in their colon. Interestingly, infected TLR-4^−/− IL-10^−/− mice displayed less compromized epithelial barrier function as indicated by lower translocation rates of live gut commensals into mesenteric lymphnodes (MLNs), and exhibited less distinct B lymphocyte responses in their colonic mucosa as compared to naїve IL-10^−/− controls. Furthermore, in extra-intestinal compartments such as MLNs and spleens, abundance of myeloid cells was less distinct whereas relative percentages of activated T helper cells and cytotoxic T cells were higher in spleens and dendritic cells more abundant in MLNs of infected IL-10^−/− animals lacking TLR-4 as compared toIL-10^−/− controls. Taken together, in conventionally colonizedIL-10^−/− mice, TLR-4, but not TLR-2, is involved in mediatingextra-intestinal pro-inflammatory immune responses following C.jejuni infection. Thus, conventional IL-10^−/− mice arewell suited to further dissect mechanisms underlyingCampylobacter infections in vivo.