Small Intestinal Pro-Inflammatory Immune Responses Following Campylobacter Jejuni Infection of Secondary Abiotic IL-10 ^–/– Mice Lacking Nucleotide-Oligomerization-Domain-2

Abstract

Host immune responses are crucial for combating enteropathogenic infections including Campylobacter jejuni. Within 1 week following peroral C. jejuni infection, secondary abiotic IL-10 ^–/– mice develop severe immunopathological sequelae affecting the colon (ulcerative enterocolitis). In the present study, we addressed whether pathogen-induced pro-inflammatory immune responses could also be observed in the small intestines dependent on the innate receptor nucleotide-oligomerization-domain-protein 2 (Nod2). Within 7 days following peroral infection, C. jejuni stably colonized the gastrointestinal tract of both IL-10 ^–/– mice lacking Nod2 (Nod2 ^–/– IL-10 ^–/–) and IL-10 ^–/– controls displaying bloody diarrhea with similar frequencies. Numbers of apoptotic and regenerating epithelial cells increased in the small intestines of C. jejuni-infected mice of either genotype that were accompanied by elevated ileal T and B lymphocyte counts. Notably, ileal T cell numbers were higher in C. jejuni-infected Nod2 ^–/– IL-10 ^–/– as compared to IL-10 ^–/– counterparts. Furthermore, multifold increased concentrations of pro-inflammatory cytokines including IFN-γ, TNF, and MCP-1 could be measured in small intestinal ex vivo biopsies derived from C. jejuni-infected mice of either genotype. In conclusion, C. jejuni-induced pro-inflammatory immune responses affected the small intestines of both Nod2 ^–/– IL-10 ^–/– and IL-10 ^–/– mice, whereas ileal T lymphocyte numbers were even higher in the former.