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.