Caspases as the key effectors of inflammatory responses against bacterial infection.

Abstract

Caspase cysteine proteases are factors widely recognized for their role in the induction of apoptotic cell death. Caspases induce apoptosis during the inflammatory response to pathogen infection; in addition, caspases such as caspase-1 and caspase-11 are known to be involved in the production of inflammatory cytokines in response to bacterial infections. Caspase-1 is activated in the inflammasome, an intracellular protein complex that is formed by the recognition of intracellular ligands or cellular stresses by sensor molecules such as NOD-like receptors. Under certain conditions, caspase-11 is required for the activation of the caspase-1 inflammasome, referred to as the non-canonical inflammasome. In addition to these caspases, accumulating evidence indicates that caspase-8 also contributes to the production of inflammatory cytokines. In contrast to caspase-1, caspase-8 is activated by receptors located on the plasma membrane including dectin-1, TLR-3/4, and Fas. Recently, Fas-mediated caspase-8 activation and inflammatory cytokine production have been shown to play a significant role in the regulation of bacterial infections. This review highlights the functional roles and activation mechanisms of caspase-1/-11 in innate immune responses against bacterial infection. In addition, we discuss the novel aspects of caspase-8 function in comparison with caspase-1/-11 during innate inflammatory responses.