Activation of an NLRP3 Inflammasome Restricts Mycobacterium kansasii Infection
Activation of an NLRP3 Inflammasome Restricts Mycobacterium kansasii Infection
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DOI：
10.1371/journal.pone.0036292
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发表时间：
2012-04-30
期刊：
影响因子：
3.7
通讯作者：
Lai, Hsin-Chih
中科院分区：
文献类型：
--
作者：
Chen, Chang-Chieh;Tsai, Sheng-Hui;Lai, Hsin-Chih
堪萨斯分枝杆菌是一种重要的非结核分枝杆菌病原体，其发病率和流行率在过去十年中呈上升趋势。M. kansasii可以引起肺结核，临床上和放射学上与由结核分枝杆菌感染引起的肺结核难以区分。与广泛研究的M.结核病，很少有人知道的先天性免疫反应，对M。堪萨斯感染。虽然炎性小体激活在宿主防御细菌感染中起重要作用，但其对非典型分枝杆菌的作用仍知之甚少。本研究探讨了THP-1巨噬细胞炎性小体活性对M. Kansasii感染进行了研究。结果表明，M. kansasii诱导巨噬细胞中caspase-1依赖性IL-1 β分泌。发现潜在的机制是通过激活含有NLR（Nod样受体）家族成员NLRP 3和接头蛋白ASC（含有CARD的骨化相关斑点样蛋白）的炎性小体。此外，钾外流、溶酶体酸化、ROS产生和组织蛋白酶B释放在M. Kansasii诱导的炎性小体激活。最后，来自半胱天冬酶-1活化的分泌的IL-1 β显示出限制细胞内M。堪萨斯。这些发现证明了NLRP 3炎性体在宿主防御M.堪萨斯。
Mycobacterium kansasii has emerged as an important nontuberculous mycobacterium pathogen, whose incidence and prevalence have been increasing in the last decade. M. kansasii can cause pulmonary tuberculosis clinically and radiographically indistinguishable from that caused by Mycobacterium tuberculosis infection. Unlike the widely-studied M. tuberculosis, little is known about the innate immune response against M. kansasii infection. Although inflammasome activation plays an important role in host defense against bacterial infection, its role against atypical mycobacteria remains poorly understood. In this report, the role of inflammasome activity in THP-1 macrophages against M. kansasii infection was studied. Results indicated that viable, but not heat-killed, M. kansasii induced caspase-1-dependent IL-1 beta secretion in macrophages. The underlying mechanism was found to be through activation of an inflammasome containing the NLR (Nod-like receptor) family member NLRP3 and the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD). Further, potassium efflux, lysosomal acidification, ROS production and cathepsin B release played a role in M. kansasii-induced inflammasome activation. Finally, the secreted IL-1 beta derived from caspase-1 activation was shown to restrict intracellular M. kansasii. These findings demonstrate a biological role for the NLRP3 inflammasome in host defense against M. kansasii.