title: Differential roles of caspase-1 and caspase-11 in infection and inflammation.
abstract: Caspase-1, also known as interleukin-1β (IL-1β)-converting enzyme (ICE), regulates antimicrobial host defense, tissue repair, tumorigenesis, metabolism and membrane biogenesis. On activation within an inflammasome complex, caspase-1 induces pyroptosis and converts pro-IL-1β and pro-IL-18 into their biologically active forms. "ICE-/-" or "Casp1-/-" mice generated using 129 embryonic stem cells carry a 129-associated inactivating passenger mutation on the caspase-11 locus, essentially making them deficient in both caspase-1 and caspase-11. The overlapping and unique functions of caspase-1 and caspase-11 are difficult to unravel without additional genetic tools. Here, we generated caspase-1-deficient mouse (Casp1Null) on the C57BL/6 J background that expressed caspase-11. Casp1Nullcells did not release IL-1β and IL-18 in response to NLRC4 activators Salmonella Typhimurium and flagellin, canonical or non-canonical NLRP3 activators LPS and ATP, Escherichia coli, Citrobacter rodentium and transfection of LPS, AIM2 activators Francisella novicida, mouse cytomegalovirus and DNA, and the infectious agents Listeria monocytogenes and Aspergillus fumigatus. We further demonstrated that caspase-1 and caspase-11 differentially contributed to the host defense against A. fumigatus infection and to endotoxemia.
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Si Ming
authors.initials: SM
authors.lastname: Man
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Karki
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Benoit
authors.initials: B
authors.lastname: Briard
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Burton
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gingras
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Stephane
authors.initials: S
authors.lastname: Pelletier
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: Thirumala-Devi
authors.initials: TD
authors.lastname: Kanneganti
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001424:Bacterial Infections / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020170:Caspase 1 / Q000235:genetics* / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D053471:Caspases, Initiator; D002478:Cells, Cultured; D005260:Female; D058847:Inflammasomes / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009181:Mycoses / Q000378:metabolism*; D000069292:Pyroptosis
chemical_list: D051017:Apoptosis Regulatory Proteins; D002135:Calcium-Binding Proteins; D058847:Inflammasomes; D036341:Intercellular Signaling Peptides and Proteins; D020382:Interleukin-18; D053583:Interleukin-1beta; C512299:Ipaf protein, mouse; D008070:Lipopolysaccharides; C588347:NLRC3 protein, mouse; C101136:Casp4 protein, mouse; D020169:Caspases; D053471:Caspases, Initiator; C000628184:Casp1 protein, mouse; D020170:Caspase 1