Microbiota Composition and Immune Responses During Campylobacter Jejuni Infection in Conventionally Colonized IL-10 ^–/– Mice Lacking Nucleotide Oligomerization Domain 2

Abstract

Host immune responses are pivotal for combating enteropathogenic infections. We here assessed the impact of the innate receptor nucleotide oligomerization domain protein 2 (NOD2) in murine Campylobacter jejuni-infection. Conventionally colonized IL-10 ^–/– mice lacking NOD2 and IL-10 ^–/– controls were perorally challenged with C. jejuni strain 81-176 and displayed comparable pathogenic colonization of intestines until day 14 postinfection (p.i.). Whereas overall intestinal microbiota compositions were comparable in naive mice, NOD2 ^–/– IL-10 ^–/– mice exhibited less fecal bifidobacteria and lactobacilli than IL-10 ^–/– counterparts after infection. Interestingly, NOD2 ^–/– IL-10 ^–/– mice were clinically more compromised during the early phase of infection, whereas, conversely, IL-10 ^–/– animals exhibited more frequently bloody feces lateron. While colonic apoptotic cell and T lymphocyte numbers were comparable in either C. jejuni-infected mice, B lymphocytes were lower in the colon of infected NOD2 ^–/– IL-10 ^–/– mice versus controls. At day 14 p.i., colonic TNF and IL-23p19 mRNA levels were upregulated in NOD2 ^–/– IL-10 ^–/– mice only. Translocation rates of intestinal commensals to mesenteric lymphnodes and extra-intestinal compartments including liver and kidney were comparable, whereas viable bacteria were more frequently detected in spleens derived from IL-10 ^–/– as compared to NOD2 ^–/– IL-10 ^–/– mice. In conclusion, NOD2 is involved during C. jejuni infection in conventionally colonized IL-10 ^–/– mice in a time-dependent manner.