title: 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.
authors.affiliation: Department of Microbiology, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan, uchiyama@hyo-med.ac.jp.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Uchiyama
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsutsui
mesh_terms: D000818:Animals; D017209:Apoptosis; D001424:Bacterial Infections / Q000201:enzymology*; D020170:Caspase 1 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007113:Immunity, Innate; D058847:Inflammasomes / Q000502:physiology*; D007249:Inflammation / Q000473:pathology*; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008024:Ligands; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000099181:Dectin-1
chemical_list: D020170:Caspase 1; D053181:Caspase 8; D020169:Caspases; D016207:Cytokines; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D037181:Lectins, C-Type; D008024:Ligands; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C546929:CLEC7A protein, human; D000099181:Dectin-1