Molecular regulation of inflammation and cell death

Abstract

Cell death and innate immunity are ancient evolutionary conserved processes that utilize a dazzling number of related molecular effectors and parallel signal transduction mechanisms. The investigation of the molecular mechanisms linking the sensing of a danger signal (pathogens or tissue damage) to the induction of an inflammatory response has witnessed a renaissance in the last few years. This was initiated by the identification of pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) and more recently cytosolic Nod-like receptors (NLRs), that brought innate immunity to center stage and opened the field to the study of signal transduction pathways, adaptors and central effectors linked to PRRs. This led to the characterization of the inflammasome, a macromolecular complex, scaffolded by NLRs, that recruits and activates inflammatory caspases, which are essential effectors in inflammation and cell death responses. In this review, we describe the molecular pathways of cell death and innate immunity with a focus on recent advancements in both fields and an emphasis on the striking analogies between NLR innate immunity and mitochondrial apoptosis pathways.