Background The nucleotide-binding oligomerisaton protein 2 (NOD2) constitutes
a pivotal sensor of bacterial muramyl dipeptide and assures expression of
distinct antimicrobial peptides and mediators produced by enterocytes and
immune cells directed against pathogens including Campylobacter jejuni. We
here elucidated the role of NOD2 during murine C. jejuni infection in more
detail. Results Conventionally colonized NOD2 deficient (NOD2−/−) mice and
corresponding wildtype (WT) counterparts were perorally infected with C.
jejuni strain 81–176 on three consecutive days. The pathogen colonized both WT
and NOD2−/− mice only sporadically until day 14 post infection (p.i.).
However, the slightly higher prevalence of C. jejuni in NOD2−/− mice was
accompanied by higher intestinal Escherichia coli loads known to facilitate C.
jejuni colonization. Neither overt macroscopic (clinical) nor microscopic
sequelae (such as colonic epithelial apoptosis) could be observed upon murine
C. jejuni infection of either genotype. Innate immune responses were less
distinctly induced in C. jejuni infected NOD2−/− versus WT mice as indicated
by lower colonic numbers of neutrophils in the former. Conversely, adaptive
immune cell counts including T lymphocytes were higher in large intestines of
NOD2−/− as compared to WT mice that were paralleled by increased colonic IL-6
secretion and higher TNF and IL-18 mRNA expression levels in large intestines
of the former. Only in NOD2−/− mice, however, colonic IL-22 mRNA expression
was down-regulated at day 14 p.i. Whereas viable commensal intestinal bacteria
could exclusively be detected in mesenteric lymph nodes and livers of NOD2−/−
mice, bacterial translocation rates to kidneys and spleen were NOD2
independent. Notably, large intestinal mRNA expression levels of mucin-2,
constituting a pivotal factor involved in epithelial barrier integrity, were
comparable in naive and C. jejuni infected mice of either genotype. Conclusion
NOD2 is involved in the well-balanced regulation of innate and adaptive pro-
inflammatory immune responses of conventional mice upon C. jejuni infection