Background Campylobacter jejuni infections are of rising importance worldwide.
Given that innate immune receptors including nucleotide-oligomerization-
domain-2 (Nod2) are essentially involved in combating enteropathogenic
infections, we here surveyed the impact of Nod2 in murine campylobacteriosis.
Methods and results In order to overcome physiological colonization resistance
preventing from C. jejuni infection, we generated secondary abiotic Nod2−/−
and wildtype (WT) mice by broad-spectrum antibiotic treatment. Mice were then
perorally infected with C. jejuni strain 81-176 on 2 consecutive days and
could be stably colonized by the pathogen at high loads. Notably, Nod2
deficiency did not affect gastrointestinal colonization properties of C.
jejuni. Despite high intestinal pathogenic burdens mice were virtually
uncompromised and exhibited fecal blood in single cases only. At day 7
postinfection (p.i.) similar increases in numbers of colonic epithelial
apoptotic cells could be observed in mice of either genotype, whereas C.
jejuni infected Nod2−/− mice displayed more distinct regenerative properties
in the colon than WT controls. C. jejuni infection was accompanied by
increases in distinct immune cell populations such as T lymphocytes and
regulatory T cells in mice of either genotype. Increases in T lymphocytes,
however, were less pronounced in large intestines of Nod2−/− mice at day 7
p.i. when compared to WT mice, whereas colonic numbers of B lymphocytes were
elevated in WT controls only upon C. jejuni infection. At day 7 p.i., colonic
pro-inflammatory mediators including nitric oxide, TNF, IFN-γ and IL-22
increased more distinctly in Nod2−/− as compared to WT mice, whereas C. jejuni
induced IL-23p19 and IL-18 levels were lower in the large intestines of the
former. Converse to the colon, however, ileal concentrations of nitric oxide,
TNF, IFN-γ, IL-6 and IL-10 were lower in Nod2−/− as compared to WT mice at day
7 p.i. Even though MUC2 was down-regulated in C. jejuni infected Nod2−/− mice,
this did not result in increased pathogenic translocation from the intestinal
tract to extra-intestinal compartments. Conclusion In secondary abiotic mice,
Nod2 signaling is involved in the orchestrated host immune responses upon C.
jejuni infection, but does not control pathogen loads in the gastrointestinal
Secondary abiotic (gnotobiotic) mice
Bacterial colonization properties
Adaptive immune cells
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit
Immune responses upon Campylobacter jejuni infection of secondary abiotic mice
Gut Pathogens. - 9 (2017), Artikel Nr. 33
Charité - Universitätsmedizin Berlin