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Activation of an NLRP3 inflammasome restricts Mycobacterium kansasii infection
PLoS One
  • Chang-Chieh Chen, Industrial Technology Research Institute
  • Sheng-Hui Tsai, National Yang-Ming University
  • Chia-Chen Lu, Fu Jen Catholic University
  • Shiau-Ting Hu, National Yang-Ming University
  • Ting-Shu Wu, Chang Gung University
  • Tsung-Teng Huang, Chang Gung University
  • Najwane Saïd-Sadier, University of California, Merced
  • David M. Ojcius, Chang Gung University
  • Hsin-Chih Lai, Chang Gung University
David M. Ojcius: 0000-0003-1461-4495
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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-1β 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-1β 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.

Article e36292
Citation Information
Chang-Chieh Chen, Sheng-Hui Tsai, Chia-Chen Lu, Shiau-Ting Hu, et al.. "Activation of an NLRP3 inflammasome restricts Mycobacterium kansasii infection" PLoS One Vol. 7 Iss. 4 (2012) p. 1 - 11 ISSN: 1932-6203
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