The NLRP3 inflammasome in tuberculosis and its regulatory mechanisms.

Tuberculosis (TB) is a severe infectious disease caused by Mycobacterium tuberculosis (Mtb). Host innate immunity plays a critical role in controlling Mtb infection, in which the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome serves as a key intracellular immune-sensing and signaling platform regulating infection-associated inflammatory responses. Activation of the NLRP3 inflammasome promotes the maturation and secretion of interleukin-1β (IL-1β) and IL-18 and induces pyroptosis, thereby exerting context-dependent dual effects in antimicrobial defense and inflammatory tissue injury. Multiple Mtb virulence factors, including ESAT-6, PPE13, and EST12, facilitate NLRP3 activation, whereas others, such as PknF, Zmp1, and Rv2569c, suppress its activity to mediate immune evasion. Moreover, NLRP3 expression and function are tightly regulated by epigenetic, transcriptional, post-transcriptional, and post-translational mechanisms. This review summarizes the structural and functional features of the NLRP3 inflammasome, highlights its activation and regulatory mechanisms in tuberculosis, and outlines recent advances in host-directed therapy (HDT) strategies targeting NLRP3, providing a theoretical basis for TB prevention and treatment.