title: Campylobacter jejuni induces extra-intestinal immune responses via Toll-like-receptor-4 signaling in conventional IL-10 deficient mice with chronic colitis.
abstract: 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 to IL-10(-/-) controls. Taken together, in conventionally colonized IL-10(-/-) mice, TLR-4, but not TLR-2, is involved in mediating extra-intestinal pro-inflammatory immune responses following C. jejuni infection. Thus, conventional IL-10(-/-) mice are well suited to further dissect mechanisms underlying Campylobacter infections in vivo.
authors.forename: B
authors.initials: B
authors.lastname: Otto
authors.forename: L-M
authors.initials: LM
authors.lastname: Haag
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: R
authors.initials: R
authors.lastname: Plickert
authors.forename: A A
authors.initials: AA
authors.lastname: Kühl
authors.forename: U B
authors.initials: UB
authors.lastname: Göbel
authors.forename: M M
authors.initials: MM
authors.lastname: Heimesaat
authors.forename: S
authors.initials: S
authors.lastname: Bereswill
keywords: Campylobacter jejuni; IL-10; TLR-2; TLR-4; chronic colitis; conventional intestinal microbiota; host–pathogen interaction; innate and adaptive immune responses; lipopeptide; lipopolysaccharide; pro-inflammatory cytokines