Mycobacterium massiliense induces inflammatory responses in macrophages through Toll-like receptor 2 and c-Jun N-terminal kinase.
Mycobacterium massiliense induces inflammatory responses in macrophages through Toll-like receptor 2 and c-Jun N-terminal kinase.
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DOI：
10.1007/s10875-013-9978-y
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发表时间：
2014-02
影响因子：
9.1
通讯作者：
Jo EK
中科院分区：
文献类型：
--
作者：
Kim TS;Kim YS;Yoo H;Park YK;Jo EK
马氏分枝杆菌 (Mmass) 是一种新兴、快速生长的分枝杆菌 (RGM)，属于脓肿分枝杆菌 (Mabc) 群，但与 Mabc 明显不同。与结核分枝杆菌（一种特征明确的人类病原体）相比，宿主针对结核分枝杆菌感染的先天免疫反应在很大程度上是未知的。在这项研究中，我们发现 Mmass 能够强有力地激活小鼠骨髓源性巨噬细胞 (BMDM) 中肿瘤坏死因子 (TNF)-α 和白细胞介素 (IL)-6 的 mRNA 和蛋白表达。 Toll 样受体 (TLR)-2 和骨髓分化初级反应基因 88 (MyD88)，但 TLR4 和 Dectin-1 都不参与 BMDM 中 Mmass 诱导的 TNF-α 或 IL-6 产生。 Mmass 感染还会激活丝裂原激活蛋白激酶（MAPK；c-Jun N 末端激酶 (JNK)、ERK1/2 和 p38 MAPK）途径。 Mmass 诱导的 TNF-α 和 IL-6 产生依赖于 JNK 激活，而它们不受 BMDM 中 ERK1/2 或 p38 途径的影响。此外，细胞内活性氧 (ROS)、NADPH 氧化酶-2 和核因子-κB 是 Mmass 诱导巨噬细胞中促炎细胞因子生成所必需的。此外，与 R 形态型相比，Mmass 的 S 形态型显示出对促炎（TNF-α、IL-6 和 IL-1β）和抗炎（IL-10）细胞因子的总体诱导较低，表明该临床菌株的免疫原性特征较少。总之，这些结果表明 Mmass 诱导的宿主促炎细胞因子的激活是通过 TLR2 依赖性 JNK 和 ROS 信号通路介导的。
Mycobacterium massiliense (Mmass) is an emerging, rapidly growing mycobacterium (RGM) that belongs to the M. abscessus (Mabc) group, albeit clearly differentiated from Mabc. Compared with M. tuberculosis, a well-characterized human pathogen, the host innate immune response against Mmass infection is largely unknown. In this study, we show that Mmass robustly activates mRNA and protein expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in murine bone marrow-derived macrophages (BMDMs). Toll-like receptor (TLR)-2 and myeloid differentiation primary response gene 88 (MyD88), but neither TLR4 nor Dectin-1, are involved in Mmass-induced TNF-α or IL-6 production in BMDMs. Mmass infection also activates the mitogen-activated protein kinase (MAPKs; c-Jun N-terminal kinase (JNK), ERK1/2 and p38 MAPK) pathway. Mmass-induced TNF-α and IL-6 production was dependent on JNK activation, while they were unaffected by either the ERK1/2 or p38 pathway in BMDMs. Additionally, intracellular reactive oxygen species (ROS), NADPH oxidase-2, and nuclear factor-κB are required for Mmass-induced proinflammatory cytokine generation in macrophages. Furthermore, the S morphotype of Mmass showed lower overall induction of pro-inflammatory (TNF-α, IL-6, and IL-1β) and anti-inflammatory (IL-10) cytokines than the R morphotype, suggesting fewer immunogenic characteristics for this clinical strain. Together, these results suggest that Mmass-induced activation of host proinflammatory cytokines is mediated through TLR2-dependent JNK and ROS signaling pathways.
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影响因子：
--
作者：
Gómez-Reino, JJ;Carmona, L;Montero, MD
通讯作者：
Montero, MD
影响因子：
15.9
作者：
Bruns, Heiko;Meinken, Christoph;Stenger, Steffen
通讯作者：
Stenger, Steffen
影响因子：
9.4
作者：
Choi, Go-Eun;Chang, Chulhun L.;Shin, Sung Jae
通讯作者：
Shin, Sung Jae
影响因子：
11.3
作者：
Gengenbacher M;Kaufmann SH
通讯作者：
Kaufmann SH
DOI：
10.1164/rccm.201003-0395oc
发表时间：
2011-02-01
影响因子：
24.7
作者：
Koh, Won-Jung;Jeon, Kyeongman;Kwon, O. Jung
通讯作者：
Kwon, O. Jung