Immunology in clinic review series; focus on autoinflammatory diseases: inflammasomes: mechanisms of activation

Initiation of a successful immune response requires a working set of sensors that detect any noxious agent within the cellular microenvironment and molecular platforms that process this signal to trigger an appropriate effector response. Pattern recognition receptors can engage different signalling cascades that lead to proinflammatory gene expression. At the same time, transcription-independent events such as activation of proteases and/or phagocytosis are also initiated. The inflammasome pathway constitutes a signalling platform that leads to the activation of so-called inflammatory caspases, most notably caspase-1, which plays a pivotal role in the cleavage and thus maturation of proinflammatory cytokines, but also in the induction of pyroptosis, a special type of cell death. In this review we elaborate on the currently known inflammasome complexes with a special focus on the mechanism behind their activation. Understanding these mechanisms could provide important information regarding the potential signalling nodes that might be targeted for therapeutic intervention.