title: Innate signaling mechanisms controlling Mycobacterium chelonae-mediated CCL2 and CCL5 expression in macrophages.
abstract: Mycobacterium chelonae (Mch) is an atypical rapidly growing mycobacterium (RGM) that belongs to the M. chelonae complex, which can cause a variety of human infections. During this type of mycobacterial infection, macrophage-derived chemokines play an important role in the mediation of intracellular communication and immune surveillance by which they orchestrate cellular immunity. However, the intracellular signaling pathways involved in the macrophage-induced chemokine production during Mch infections remain unknown. Thus, the present study aimed to determine the molecular mechanisms by which Mch activates the gene expressions of chemokine (C-C motif) ligand 2 (CCL2) and CCL5 in murine bone marrow-derived macrophages (BMDMs) and in vivo mouse model. Toll-like receptor 2 (TLR2)-deficient mice showed increased bacterial burden in spleen and lung and decreased protein expression of CCL2 and CCL5 in serum. Additionally, Mch infection triggered the mRNA and protein expression of CCL2 and CCL5 in BMDMs via TLR2 and myeloid differentiation primary response gene 88 (MyD88) signaling and that it rapidly activated nuclear factor (NF)-κB signaling, which is required for the Mch-induced expressions of CCL2 and CCL5 in BMDMs. Moreover, while the innate receptor Dectin-1 was only partly involved in the Mch-induced expression of the CCL2 and CCL5 chemokines in BMDMs, the generation of intracellular reactive oxygen species (ROS) was an important contributor to these processes. Taken together, the present data indicate that the TLR2, MyD88, and NF-κB pathways, Dectin-1 signaling, and intracellular ROS generation contribute to the Mch-mediated expression of chemokine genes in BMDMs.
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea.|Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea.
authors.forename: Yi Sak
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Infection Biology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea.|Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Institute Pasteur Korea, Seongnam, 13488, Republic of Korea.
authors.forename: Minjeong
authors.initials: M
authors.lastname: Woo
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea.|Infection Biology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea.
authors.forename: Tae-sung
authors.initials: TS
authors.lastname: Kim
authors.affiliation: Division of Infectious Diseases, Chungnam National University Hospital, Daejeon, 34134, Republic of Korea.
authors.forename: Kyung Mok
authors.initials: KM
authors.lastname: Sohn
authors.affiliation: Infection Biology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea.|Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea.
authors.forename: Young-Ha
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea.|Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea.
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
authors.affiliation: Infection Biology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea. yjaemin0@cnu.ac.kr.|Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea. yjaemin0@cnu.ac.kr.
authors.forename: Jae-Min
authors.initials: JM
authors.lastname: Yuk
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology*; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D007111:Immunity, Cellular; D007113:Immunity, Innate; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009165:Mycobacterium Infections, Nontuberculous / Q000276:immunology*; D016926:Mycobacterium chelonae / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099181:Dectin-1
chemical_list: D018932:Chemokine CCL2; D018946:Chemokine CCL5; D037181:Lectins, C-Type; D053594:Myeloid Differentiation Factor 88; D052002:NF-kappa B p50 Subunit; D017382:Reactive Oxygen Species; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D000099181:Dectin-1; C491768:Ccl2 protein, mouse; C503460:Ccl5 protein, mouse; C507780:Myd88 protein, mouse; C493486:Tlr2 protein, mouse; C073701:Nfkb1 protein, mouse
keywords: MyD88; Mycobacterium chelonae; NF-κB; ROS; TLR2; chemokine; dectin-1; macrophages