PMID- 26626357 OWN - NLM STAT- MEDLINE DCOM- 20160906 LR - 20181113 IS - 1976-3794 (Electronic) IS - 1225-8873 (Linking) VI - 53 IP - 12 DP - 2015 Dec TI - Innate signaling mechanisms controlling Mycobacterium chelonae-mediated CCL2 and CCL5 expression in macrophages. PG - 864-74 LID - 10.1007/s12275-015-5348-1 [doi] AB - 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)-kappaB 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-kappaB pathways, Dectin-1 signaling, and intracellular ROS generation contribute to the Mch-mediated expression of chemokine genes in BMDMs. FAU - Kim, Yi Sak AU - Kim YS AD - Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea. AD - Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea. FAU - Kim, Ji Hye AU - Kim JH AD - Infection Biology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea. AD - Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea. FAU - Woo, Minjeong AU - Woo M AD - Institute Pasteur Korea, Seongnam, 13488, Republic of Korea. FAU - Kim, Tae-sung AU - Kim TS AD - Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea. AD - Infection Biology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea. FAU - Sohn, Kyung Mok AU - Sohn KM AD - Division of Infectious Diseases, Chungnam National University Hospital, Daejeon, 34134, Republic of Korea. FAU - Lee, Young-Ha AU - Lee YH AD - Infection Biology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea. AD - Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea. FAU - Jo, Eun-Kyeong AU - Jo EK AD - Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea. AD - Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea. FAU - Yuk, Jae-Min AU - Yuk JM AD - Infection Biology, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea. yjaemin0@cnu.ac.kr. AD - Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon, 34134, Republic of Korea. yjaemin0@cnu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151202 PL - Korea (South) TA - J Microbiol JT - Journal of microbiology (Seoul, Korea) JID - 9703165 RN - 0 (Ccl2 protein, mouse) RN - 0 (Ccl5 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Chemokine CCL5) RN - 0 (Lectins, C-Type) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (NF-kappa B p50 Subunit) RN - 0 (Reactive Oxygen Species) RN - 0 (Tlr2 protein, mouse) RN - 0 (Toll-Like Receptor 2) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (dectin 1) RN - 147257-52-1 (Nfkb1 protein, mouse) SB - IM MH - Animals MH - Chemokine CCL2/genetics/*immunology MH - Chemokine CCL5/genetics/*immunology MH - Disease Models, Animal MH - Immunity, Cellular MH - *Immunity, Innate MH - Lectins, C-Type/metabolism MH - Macrophages/*immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mycobacterium Infections, Nontuberculous/*immunology MH - Mycobacterium chelonae/*immunology MH - Myeloid Differentiation Factor 88/genetics/metabolism MH - NF-kappa B p50 Subunit/metabolism MH - Reactive Oxygen Species/immunology/metabolism MH - Signal Transduction/immunology MH - Toll-Like Receptor 2/genetics/metabolism MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - MyD88 OT - Mycobacterium chelonae OT - NF-kappaB OT - ROS OT - TLR2 OT - chemokine OT - dectin-1 OT - macrophages EDAT- 2015/12/03 06:00 MHDA- 2016/09/07 06:00 CRDT- 2015/12/03 06:00 PHST- 2015/06/14 00:00 [received] PHST- 2015/11/19 00:00 [accepted] PHST- 2015/10/27 00:00 [revised] PHST- 2015/12/03 06:00 [entrez] PHST- 2015/12/03 06:00 [pubmed] PHST- 2016/09/07 06:00 [medline] AID - 10.1007/s12275-015-5348-1 [pii] AID - 10.1007/s12275-015-5348-1 [doi] PST - ppublish SO - J Microbiol. 2015 Dec;53(12):864-74. doi: 10.1007/s12275-015-5348-1. Epub 2015 Dec 2.