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UID:20250810T072106EDT-5002vTILlg@132.216.98.100
DTSTAMP:20250810T112106Z
DESCRIPTION:Intracellular lipopolysaccharide (LPS) from Gram-negative bacte
 ria including Escherichia coli\, Salmonella typhimurium\, Shigella flexner
 i\, and Burkholderia thailandensis activates mouse caspase-11 causing pyro
 ptotic cell death\, IL-1b processing\, and lethal septic shock. How caspas
 e-11 drives these downstream signaling events is largely unknown. Here we 
 show that Gasdermin-D (Gsdmd) is essential for caspase-11-dependent pyropt
 osis and IL-1b maturation. A forward genetic screen with ethyl-N-nitrosour
 ea-mutagenized mice linked Gsdmd to the intracellular LPS response. Macrop
 hages from Gsdmd–/– mice generated by gene targeting also exhibited defect
 ive pyroptosis and IL-1b secretion induced by cytoplasmic LPS or Gram-nega
 tive bacteria. In addition\, Gsdmd–/–  mice were protected from a lethal d
 ose of LPS. Mechanistically\, caspase-11 cleaved Gsdmd and the N-terminal 
 Gsdmd fragment promoted both pyroptosis and NLRP3-dependent activation of 
 caspase-1 in a cell-intrinsic manner. Our data identify Gsdmd as a critica
 l target of caspase-11 and a key mediator of the host response against Gra
 m-negative bacterial infection. At the meeting I’ll give an update on the 
 discovery of an additional mediator of pyroptosis: IRF2\, a transcriptiona
 l factor that drives the expression of Gsdmd. In it’s absence cells and mi
 ce are resistant to LPS challenge. In sum we have defined a new pathway fo
 r LPS responsiveness that may have therapeutic potential.\n\nThis seminar 
 will be given online via Zoom. Details in attached poster.\n
DTSTART:20211022T150000Z
DTEND:20211022T160000Z
SUMMARY:Online Seminar: The non-canonical Inflammasome Pathway
URL:/physiology/channels/event/online-seminar-non-cano
 nical-inflammasome-pathway-333918
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