Figure 2.

Proposed model of inflammasome-mediated pathogenesis of TB-IRIS. (1–2) In a microenvironment with low levels of IFN-γ, by interfering with the phagosome-lysosome fusion, MTB can evade the monocyte/macrophage bactericidal effectors [89] thereby continuing intracellular replication [90] leading to mitochondrial stress [91]. (3) Intracellular MTB accumulation and mtDNA result results inNLRP3 and AIM2 inflammasome assembly and activation of casp1. (4–5) In order to become active, the inactive form (pro-IL 18) of the potent pro-inflammatory cytokine IL-18 must first be processed by casp1 (6–9) In addition to processing IL-18, casp1 also promotes pyroptosis, an inflammatory form of programmed cell death. Pyroptosis results in the expulsion of mtDNA into the bloodstream which in turn amplifies inflammatory responses. (10) IFN-γ and NO negatively regulate NLRP3 and AIM2.