The intricate interactions between inflammasomes and bacterial pathogens: Roles, mechanisms, and therapeutic potentials

Abstract

Inflammasomes are intracellular multiprotein complexes that consist of a sensor, an adaptor, and a caspase enzyme to cleave interleukin (IL)-1β and IL-18 into their mature forms. In addition, caspase-1 and -11 activation results in the cleavage of gasdermin D to form pores, thereby inducing pyroptosis. Activation of the inflammasome and pyroptosis promotes host defense against pathogens, whereas dysregulation of the inflammasome can result in various pathologies. Inflammasomes exhibit versatile microbial signal detection, directly or indirectly, through cellular processes, such as ion fluctuations, reactive oxygen species generation, and the disruption of intracellular organelle function; however, bacteria have adaptive strategies to manipulate the inflammasome by altering microbe-associated molecular patterns, intercepting innate pathways with secreted effectors, and attenuating inflammatory and cell death responses. In this review, we summarize recent advances in the diverse roles of the inflammasome during bacterial infections and discuss how bacteria exploit inflammasome pathways to establish infections or persistence. In addition, we highlight the therapeutic potential of harnessing bacterial immune subversion strategies against acute and chronic bacterial infections. A more comprehensive understanding of the significance of inflammasomes in immunity and their intricate roles in the battle between bacterial pathogens and hosts will lead to the development of innovative strategies to address emerging threats posed by the expansion of drug-resistant bacterial infections.

Keywords: Bacterial infections; Immunity; Inflammasomes; Pyroptosis; Therapeutics.