title: The Nod2 sensor promotes intestinal pathogen eradication via the chemokine CCL2-dependent recruitment of inflammatory monocytes.
abstract: The intracellular sensor Nod2 is activated in response to bacteria, and the impairment of this response is linked to Crohn's disease. However, the function of Nod2 in host defense remains poorly understood. We found that Nod2-/- mice exhibited impaired intestinal clearance of Citrobacter rodentium, an enteric bacterium that models human infection by pathogenic Escherichia coli. The increased bacterial burden was preceded by reduced CCL2 chemokine production, inflammatory monocyte recruitment, and Th1 cell responses in the intestine. Colonic stromal cells, but not epithelial cells or resident CD11b+ phagocytic cells, produced CCL2 in response to C. rodentium in a Nod2-dependent manner. Unlike resident phagocytic cells, inflammatory monocytes produced IL-12, a cytokine that induces adaptive immunity required for pathogen clearance. Adoptive transfer of Ly6C(hi) monocytes restored the clearance of the pathogen in infected Ccr2-/- mice. Thus, Nod2 mediates CCL2-CCR2-dependent recruitment of inflammatory monocytes, which is important in promoting bacterial eradication in the intestine.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Yun-Gi
authors.initials: YG
authors.lastname: Kim
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kamada
authors.forename: Michael H
authors.initials: MH
authors.lastname: Shaw
authors.forename: Neil
authors.initials: N
authors.lastname: Warner
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Chen
authors.forename: Luigi
authors.initials: L
authors.lastname: Franchi
authors.forename: Gabriel
authors.initials: G
authors.lastname: Núñez
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000276:immunology*; D044082:Citrobacter rodentium / Q000276:immunology*; D003092:Colitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D004756:Enterobacteriaceae Infections / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology*; D017154:Stromal Cells / Q000276:immunology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse