Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 210, Issue 7, Pages 1145-1154Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiu148
Keywords
innate immunity; intestinal inflammation; campylobacteriosis; bactericide; Il10(-/-) mice
Categories
Funding
- National Institutes of Health [DK047700, DK073338, AI082319, P30 DK34987]
Ask authors/readers for more resources
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-1 beta, Tnf alpha, 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available