title: Nucleotide-binding oligomerization domain 2 (Nod2) is dispensable for the innate immune responses of macrophages against Yersinia enterocolitica.
abstract: Nucleotide-binding oligomerization domain 2 (Nod2) is a cytosolic sensor for muramyl dipeptide, a component of bacterial peptidoglycan. In this study, we have examined whether Nod2 mediates the immune response of macrophages against Yersinia enterocolitica. Bone-marrow-derived macrophages (BMDMs) were isolated from WT and Nod2-deficient mice and were infected with various strains of Y. enterocolitica. ELISA showed that the production of IL-6 and TNF-α in BMDMs infected with Y. enterocolitica was not affected by the Nod2 deficiency. iNOS mRNA expression was induced in both WT and Nod2-deficienct BMDMs in response to Y. enterocolitica, beginning 2 h after infection. Nitric oxide (NO) production by Y. enterocolitica did not differ between WT and Nod2-deficient BMDMs. Western blot analysis revealed that Y. enterocolitica induces activation of NF-κB, p38, and ERK MAPK through a Nod2-independent pathway. Neither LDH release by Y. enterocolitica nor the phagocytic activity of the macrophages was altered by Nod2 deficiency. An in vivo experiment showed that bacterial clearance ability and production of IL-6 and KC in serum were comparable in WT and Nod2-deficient mice infected with Y. enterocolitica. These findings suggest that Nod2 may not be critical for initiating the innate immune response of macrophages against Yersinia infection.
authors: Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 302-711, Republic of Korea.
authors: Yu-Jin
authors: YJ
authors: Jeong
authors: Chang-Hwan
authors: CH
authors: Kim
authors: Eun-Jung
authors: EJ
authors: Song
authors: Min-Jung
authors: MJ
authors: Kang
authors: Jee-Cheon
authors: JC
authors: Kim
authors: Sang-Muk
authors: SM
authors: Oh
authors: Kyung-Bok
authors: KB
authors: Lee
authors: Jong-Hwan
authors: JH
authors: Park
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015009:Yersinia Infections / Q000276:immunology / Q000473:pathology; D015008:Yersinia enterocolitica / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse