The Inflammasome: Regulation of Nitric Oxide and Antimicrobial Host Defence

Nitric oxide (NO) is a gaseous signalling molecule that plays diverse physiological functions including antimicrobial host defence. During microbial infection, NO is synthesized by inducible NO synthase (iNOS), which is expressed by host immune cells through the recognition of microbial pattern molecules. Therefore, sensing pathogens or their pattern molecules by pattern recognition receptors (PRRs), which are located at the cell surface, endosomal and phagosomal compartment, or in the cytosol, is key in inducing iNOS and eliciting antimicrobial host defence. A group of cytosolic PRRs is involved in inducing NO and other antimicrobial molecules by forming a molecular complex called the inflammasome. Assembled inflammasomes activate inflammatory caspases, such as caspase-1 and caspase-11, which in turn process proinflammatory cytokines IL-1β and IL-18 into their mature forms and induce pyroptotic cell death. IL-1β and IL-18 play a central role in immunity against microbial infection through activation and recruitment of immune cells, induction of inflammatory molecules, and regulation of antimicrobial mediators including NO. Interestingly, NO can also regulate inflammasome activity in an autocrine and paracrine manner. Here, we discuss molecular mechanisms of inflammasome formation and the inflammasome-mediated regulation of host defence responses during microbial infections.