| Title | Innate signaling mechanisms controlling Mycobacterium chelonae-mediated CCL2 and CCL5 expression in macrophages |
|---|---|
| Author | Yi Sak Kim1,2, Ji Hye Kim2,3, Minjeong Woo4, Tae-sung Kim Kim1,3, Kyung Mok Sohn5, Young-Ha Lee2,3, Eun-Kyeong Jo1,2, and Jae-Min Yuk2,3* |
| Address | 1Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 34134, Republic of Korea, 2Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon 34134, Republic of Korea, 3Department of Infection Biology, College of Medicine, Chungnam National University, Daejeon 34134, Republic of Korea, 4Institute Pasteur Korea, Seongnam 13488, Republic of Korea, 5Division of Infectious Diseases, Chungnam National University Hospital, Daejeon 34134, Republic of Korea |
| Bibliography | Journal of Microbiology, 53(12),864-874, 2015, |
| DOI | 10.1007/s12275-015-5348-1 |
| Key Words | Mycobacterium chelonae, macrophages, chemokine, TLR2, MyD88, dectin-1, ROS, NF-κB |
| 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, macrophagederived 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. |