Apoptosis, Cell Death and Inflammation

ceptors (e.g. members of the TNF superfamily such as TNFR1, CD95 or Toll-like receptors [4] ), or the intracellular sensors, nucleotide-binding and oligomerization domain (NOD)-like receptors [5, 6] , all of which can instigate inflammatory responses and modulate the cell’s survival/death balance. NOD-like receptors can assemble into large multiprotein complexes, termed inflammasomes, which can activate caspase-1, a proteolytic enzyme that cleaves and activates the secreted cytokines interleukin-1 and interleukin-18, thereby initiating an inflammatory response [7] . The review by Yazdi et al. [8] provides a comprehensive overview of the inflammasome, caspase-1 activation and how this protein complex is regulated. Diverse endogenous, microbial or chemical stimuli activate that oligomeric protein platform, thereby initiating inflammatory cell recruitment and engagement. Inflammasomes are essential regulators of inflammation and their dysregulation has clinical implications. Notably, activated caspase-1 can also trigger pyroptosis, a form of cell death with necrosis, whose most prominent morphological feature is the loss of plasma membrane integrity, with liberation of the cytoplasm’s highly inflammatory contents into the extracellular medium, thereby emphasizing the distinct form and function of this programmed cell death [9] . It has become apparent that cells also combat infection by activating autophagy, an alternative route to the digestive lysosomes [10] . Neutrophils and monocytes/macrophages, professional phagocytic cells, are key anti-infectious actors in host defense but are also inflammatory cells able to mediThis issue of the Journal of Innate Immunity is devoted to exploring ‘Apoptosis, cell death and innate immunity’ and aims to spotlight a few selected issues that might provide future opportunities to modulate inflammation. Infections elicit diverse host responses that include activation of the innate immune system, inflammation and programmed cell death, which is a pivotal process that tailors host–pathogen interactions. The mechanisms of pathogen-induced cell death often involve modulation of the apoptotic response, as has been demonstrated in neutrophils [1] . Apoptosis, the best-described form of programmed cell death, is mediated by the caspases, which are cysteinyl aspartate-specific proteinases. Initiator (2, 8, 9 and 10) and effector (3, 6 and 7) [2] caspase family members are involved in various cell death events: mitochondrial outer membrane permeabilization, cytochrome c and Smac/DIABLO (second mitochondrion-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low p) release into the cytosol, DNA fragmentation, chromatin condensation, loss of membrane asymmetry, apoptotic body formation and generation of ‘eat-me signals’ that stimulate apoptotic cell phagocytosis by macrophages or surrounding cells. Because the cytoplasmic contents of apoptotic cells are not spilled into the extracellular medium, apoptosis does not trigger an inflammatory response and, hence, is considered immunologically silent [3] . Cell survival during infection or tissue injury is regulated by integrating different pathways via immune rePublished online: March 16, 2010 Journal of Innate Immunity