Absence of Nucleotide-Oligomerization-Domain-2 Is Associated with Less Distinct Disease in Infected Secondary Abiotic IL-10 Deficient Mice.

Human -infections are progressively increasing worldwide. Despite their high prevalence and socioeconomic impact the underlying mechanisms of pathogen-host-interactions are only incompletely understood. Given that the innate immune receptor nucleotide-oligomerization-domain-2 (Nod2) is involved in clearance of enteropathogens, we here evaluated its role in murine campylobacteriosis. To address this, we applied Nod2-deficient IL-10 (Nod2 IL-10) mice and IL-10 counterparts both with a depleted intestinal microbiota to warrant pathogen-induced enterocolitis. At day 7 following peroral strain 81-176 infection, Nod2 mRNA was down-regulated in the colon of secondary abiotic IL-10 and wildtype mice. Nod2-deficiency did neither affect gastrointestinal colonization nor extra-intestinal and systemic translocation properties of . Colonic mucin-2 mRNA was, however, down-regulated upon -infection of both Nod2 IL-10 and IL-10 mice, whereas expression levels were lower in infected, but also naive Nod2 IL-10 mice as compared to respective IL-10 controls. Remarkably, -infected Nod2 IL-10 mice were less compromised than IL-10 counterparts and displayed less distinct apoptotic, but higher regenerative cell responses in colonic epithelia. Conversely, innate as well as adaptive immune cells such as macrophages and monocytes as well as T lymphocytes and regulatory T-cells, respectively, were even more abundant in large intestines of Nod2 IL-10 as compared to IL-10 mice at day 7 post-infection. Furthermore, IFN-γ concentrations were higher in biopsies derived from intestinal compartments including colon and mesenteric lymph nodes as well as in systemic tissue sites such as the spleen of infected Nod2 IL-10 as compared to IL10 counterparts. Whereas, at day 7 postinfection anti-inflammatory IL-22 mRNA levels were up-regulated, IL-18 mRNA was down-regulated in large intestines of Nod2 IL-10 vs. IL-10 mice. In summary, -infection induced less clinical signs and apoptosis, but more distinct colonic pro- and (of note) anti-inflammatory immune as well as regenerative cell responses in Nod2 deficient IL-10 as compared to IL-10 control mice. We conclude that, even though colonic Nod2 mRNA was down-regulated upon pathogenic challenge, Nod2-signaling is essentially involved in the well-balanced innate and adaptive immune responses upon -infection of secondary abiotic IL-10 mice, but does neither impact pathogenic colonization nor translocation.