FIG 2.

Mechanisms of host and pathogen cross-regulation of IL-1 during M. tuberculosis infection. On the host side, type I IFNs are major regulators of IL-1 responses, acting directly by inhibiting the transcription of pro-IL-1β or indirectly by inducing IL-10, which downregulates the expression of pro-IL-1β, or upregulating IL-1R2 and IL-1RA. TIR8/SIGIRR also blocks IL-1R responses. PGE₂ induced by IL-1β counterregulates the action of type I IFN by blocking its transcription. At the posttranscriptional level, NO regulates the production of IL-1 by inhibiting the NLRP3 inflammasome. On the pathogen side, M. tuberculosis (Mtb) has evolved multiple mechanisms to downregulate IL-1β, from blocking macrophage glycolytic reprogramming to blocking the inflammasome. Genetically diverse clinical isolates of M. tuberculosis have been shown to modulate the production of IL-1β via impacting inflammasome activity. MDR, multidrug resistant.