Discussion

Inflammasomes are multimeric protein complexes that assemble in the cytosol of many types of cells, including innate immune cells. The inflammasomes can be activated in response to infection or in response to stress signals that induce damage in the host cell membranes. These platforms trigger inflammatory processes, cell death, and the control of microbial replication. Many inflammasomes have been described so far, including NLRP3, NAIP/NLRC4, caspase-11, and AIM2. The ligand for NLRP3 is still unidentified, but the efflux of K+ is essential for NLRP3 activation. By contrast, inflammasomes, such as those composed of NAIP/NLRC4, caspase-11, and AIM2, can be activated by bacterial flagellin, LPS, and dsDNA. The knowledge of inflammasome biology in response to bacteria has advanced tremendously in the last decade, while inflammasome activation in response to intracellular parasites, remains less explored. Leishmania infection triggers activation of the NLRP3 inflammasome in macrophages for restriction of intracellular parasite replication. Accordingly, Leishmania can dampen NLRP3 activation as an evasion strategy. In vivo, the NLRP3 inflammasome can promote parasite clearance, but the failure to eliminate parasites in the tissues together with sustained inflammasome activation can promote IL-1β-mediated disease pathology. Data to be presented will highlight recent data regarding activation and consequences of inflammasome activation in response to Leishmania, a process that effectively impacts the development of the disease in humans.