Figure 4. Caspase 1 activation in health and disease: fighting infection versus pathological inflammation.
Caspase 1 plays a protective part in the response to microbial infection. a | In response to infection, quiescent cells undergo caspase 1 activation and pyroptosis, allowing cleavage and release of interleukin-18 (IL-18), IL-1β and other inflammatory intracellular contents. Quiescent cells can also undergo ‘activation’ in response to inflammatory mediators, thereby lowering the threshold for caspase 1 activation and pyroptosis and stimulating increased production of IL-1β. b | As infection progresses, the inflammation that occurs as a consequence of pyroptosis leads to an increased population of activated cells that are primed to undergo pyroptosis and have increased inflammatory potential. c | Inflammatory contents produced during pyroptosis recruit and activate immune cells and stimulate the development of adaptive immune responses. This contributes to the control and ultimate resolution of microbial infection, and returns tissues to their resting state. Alternatively, caspase 1 activation can be detrimental, as mutations in Nod-like receptor (NLR) proteins or the persistence of sterile inflammatory stimuli can result in inappropriate and/or excessive caspase 1 activation. The inflammation produced by this process increases the population of activated cells that are primed to undergo pyroptosis and express increased levels of IL-1β, and the amplification cycle persists (b). This potentiates the response and maintains an inflammatory state, which, if uninterrupted, leads to pathology.