AbstractMycobacterium leprae is the organism responsible for causing leprosy, a persistent contagious illness. The inflammasome is a complex of cytosolic proteins that mediates the inflammatory response in response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), the latter of which is responsible for the maturation of caspase 1, secretion of IL-1 and IL-18, and a type of cell death known as pyroptosis. One protein, interleukin-1 conversion enzyme (ICE)-protease activating factor, was found to be responsible for initiating caspase-1. (IPAF). The amino-terminal CARD domain and its surrounding amino acids confirmed its membership in the NLR protein family, prompting the nomenclature change to NLRC4. In reaction to bacterial infections that target the cytoplasm of host cells, like M. tuberculosis and M. leprae, new data indicates that the NLRP3 inflammasome is involved in the inflammatory response caused by caspase-11. Activation of the NLRP3 inflammasome follows a classical pathway that begins with the recognition of PAMPs or DAMPs by TLRs, which then activates nuclear factor kappa B (NF-B)-mediated signaling and up-regulates transcription of inactive NLRP3, pro-IL-1, and pro-IL-18. Oligomerization of NLRP3 is the second stage, which is then followed by the formation of a complex containing NLRP3, ASC, and pro-caspase-1. This results in the synthesis and release of mature IL-1 and IL-18, as well as the self-activation of pro-caspase-1 into the enzymatically active form by proteolytic cleavage. The clinical course of an infection depends on the result of this first interaction, and it now appears that NLRP1, NLRP3, caspase 1, IL-1, and IL-18 collaborate in a concerted effort to trigger this early reaction.
