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J Infect Dis. 2014 Oct 1;210(7):1145-54. doi: 10.1093/infdis/jiu148. Epub 2014 Mar 11.

Nucleotide-binding oligomerization domain-containing protein 2 controls host response to Campylobacter jejuni in Il10-/- mice.

Author information

1
Department of Medicine.
2
Department of Medicine Infectious Diseases and Pathology, University of Florida, Gainesville.

Abstract

Innate signaling-induced antimicrobial response represents a key protective host feature against infectious microorganisms such as Campylobacter species. In this study, we investigated the role of nucleotide-binding oligomerization domain-containing protein 2 (NOD2) in Campylobacter jejuni-induced intestinal inflammation. Specific-pathogen-free Il10(-/-), Nod2(-/-), and Il10(-/-); Nod2(-/-) mice were infected with C. jejuni (10(9) colony-forming units/mouse) 24 hours after a 7-day course of antibiotic treatment. Three weeks later, host responses were determined. The nitric oxide (NO) donor sodium nitroprusside was injected intraperitoneally (2 mg/kg daily) to supplement NO. Although healthy in specific-pathogen-free conditions, Il10(-/-); Nod2(-/-) mice developed severe intestinal inflammation following C. jejuni infection, compared with Nod2(-/-) and Il10(-/-) mice. The onset of colitis was associated with elevated neutrophil accumulation, crypt abscesses, and expression of the endogenous proinflammatory mediators Il-1β, Tnfα, and Cxcl1. Fluorescence in situ hybridization and culture assay showed enhanced C. jejuni invasion into the colon and mesenteric lymph nodes in Il10(-/-); Nod2(-/-) mice, compared with Il10(-/-) mice. C. jejuni-induced bactericidal NO production was reduced in peritoneal macrophages from Il10(-/-); Nod2(-/-) mice, compared with Il10(-/-) mice. Importantly, sodium nitroprusside attenuated C. jejuni-induced colitis in Il10(-/-); Nod2(-/-) mice. Our findings suggest that NOD2 signaling is critical to control campylobacteriosis in Il10(-/-) mice, a process involving NOD2-mediated bactericidal responses.

KEYWORDS:

Il10−/−mice; bactericide; campylobacteriosis; innate immunity; intestinal inflammation

PMID:
24620022
PMCID:
PMC4168300
DOI:
10.1093/infdis/jiu148
[Indexed for MEDLINE]
Free PMC Article

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