title: Mycobacterium fortuitum induces A20 expression that impairs macrophage inflammatory responses.
abstract: Mycobacterium fortuitum is a rapidly growing mycobacterium that has been regarded as an etiological agent of a variety of human infections. However, little is known about the host inflammatory responses and the molecular mechanisms by which MF-induced inflammation is regulated in macrophages. In this study, we report that MF infection leads to the induction of an anti-inflammatory molecule, A20 (also known as TNFAIP3), which is essential for the regulation of MF-induced inflammatory responses in murine bone marrow-derived macrophages (BMDMs). MF triggered the expression of tumor necrosis factor-α and interleukin-6 in BMDMs through signaling of the Toll-like receptor 2 (TLR2)-myeloid differentiation primary response gene 88. Additionally, MF rapidly induced the expression of A20, which inhibited proinflammatory cytokine expression and nuclear factor (NF)-κB reporter gene activities in BMDMs. Notably, MF-induced activation of NF-κB signaling was required for A20 expression and proinflammatory responses in BMDMs. Furthermore, the rough morphotype of the MF clinical strain induced a higher level of proinflammatory signaling activation, but less A20 induction in BMDMs, compared to the smooth morphotype. Taken together, these results suggest that MF-induced activation of host proinflammatory responses is negatively regulated through TLR2-dependent A20 expression.
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Gippeum Joy
authors.initials: GJ
authors.lastname: Lee
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Hye-Mi
authors.initials: HM
authors.lastname: Lee
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Division of Infectious Diseases, Chungnam National University Hospital, Daejeon 35015, South Korea.
authors.forename: Kyung Mok
authors.initials: KM
authors.lastname: Sohn
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea hayoungj@cnu.ac.kr.
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009165:Mycobacterium Infections, Nontuberculous / Q000276:immunology* / Q000382:microbiology; D019907:Mycobacterium fortuitum / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051996:Transcription Factor RelA / Q000276:immunology; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D034741:RNA, Small Interfering; C498144:Rela protein, mouse; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse
keywords: A20; MyD88; Mycobacterium fortuitum; NF-κB; TLR; proinflammatory cytokines