title: Pyroptotic death storms and cytopenia.
abstract: For over two decades, we have embraced the cytokine storm theory to explain sepsis, severe sepsis and septic shock. The failure of numerous large-scale clinical trials, which aimed to treat sepsis by neutralizing inflammatory cytokines and LPS, indicates that alternative pathophysiological mechanisms are likely to account for sepsis and the associated immune suppression in patients with severe infection. Recent insights that extricate pyroptotic death from inflammatory cytokine production in vivo have highlighted a need to investigate the consequences of apoptotic and non-apoptotic death in contributing to cytopenia and immune suppression. In this review, we will focus on the biochemical and cellular mechanisms controlling pyroptosis, a Caspase-1/11 dependent form of cell death during infection.
authors.affiliation: Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address: ben.croker@childrens.harvard.edu.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Croker
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: Joanne A
authors.initials: JA
authors.lastname: O'Donnell
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
authors.forename: Motti
authors.initials: M
authors.lastname: Gerlic
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D020170:Caspase 1 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D053471:Caspases, Initiator; D016923:Cell Death / Q000276:immunology; D057899:Cytophagocytosis / Q000276:immunology; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D016867:Immunocompromised Host; D058847:Inflammasomes / Q000096:biosynthesis / Q000378:metabolism; D020382:Interleukin-18 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D051379:Mice; D009336:Necrosis; D013379:Substrate Specificity / Q000276:immunology; D018746:Systemic Inflammatory Response Syndrome / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*
chemical_list: D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; C101136:Casp4 protein, mouse; D020169:Caspases; D053471:Caspases, Initiator; D020170:Caspase 1