Abstract

VARIOUS SOURCES OF INFLAMMASOME FORMATION: AN OVERVIEW

Naresh Kshirasagar, G. Harika, T. Shalini, Srilatha Malvey*

Abstract

Inflammasome are multipotent complexes that play a crucial role in the innate immune response by sensing a wide array of pathogenic and sterile stimuli. Upon activation, these cytosolic sensors initiate caspase-1 activation, leading to the maturation and secretion of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-18 (IL-18), and the induction of pyroptosis, an inflammatory form of cell death. Numerous inflammasome types have been identified, including NLRP3, NLRC4, AIM2, NLRP1, and Pyrin, each recognizing distinct triggers. These triggers originate from diverse sources such as pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), environmental irritants, metabolic disturbances, and endogenous stress signals. For instance, bacterial toxins, viral nucleic acids, extracellular ATP, uric acid crystals, and mitochondrial dysfunction are wellestablished activators. Among these, the NLRP3 inflammasome is the most extensively studied due to its sensitivity to a broad spectrum of stimuli and its involvement in numerous inflammatory, autoimmune, and metabolic diseases. Understanding the various sources and mechanisms of inflammasome activation provides critical insights into host defense and disease pathogenesis. Furthermore, it opens new avenues for therapeutic interventions targeting aberrant inflammasome activity. This review provides a comprehensive overview of the known sources of inflammasome formation, highlighting their molecular mechanisms and clinical implications in health and disease.

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