title: Nucleotide-binding oligomerization domain-containing protein 2 controls host response to Campylobacter jejuni in Il10-/- mice.
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.
authors.affiliation: Department of Medicine.
authors.forename: Xiaolun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Medicine Infectious Diseases and Pathology, University of Florida, Gainesville.
authors.forename: Christian
authors.initials: C
authors.lastname: Jobin
mesh_terms: D000818:Animals; D002169:Campylobacter Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D016123:Campylobacter jejuni / Q000276:immunology*; D003092:Colitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D003106:Colon / Q000382:microbiology / Q000473:pathology; D016753:Interleukin-10 / Q000172:deficiency*; D008198:Lymph Nodes / Q000382:microbiology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C556062:IL10 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D016753:Interleukin-10; D009569:Nitric Oxide
keywords: Il10−/−mice; bactericide; campylobacteriosis; innate immunity; intestinal inflammation