biostudies-literatureBjanes EChildren's Hospital of PhiladelphiaBurroughs Wellcome FundNIAID NIH HHSNHLBI NIH HHSDivision of Intramural Research, National Institute of Allergy and Infectious Diseasese1009967https://www.ebi.ac.uk/biostudies/studies/S-EPMC8547626biostudies-literatureUnknown17(10)Cell death plays a critical role in inflammatory responses. During pyroptosis, inflammatory caspases cleave Gasdermin D (GSDMD) to release an N-terminal fragment that generates plasma membrane pores that mediate cell lysis and IL-1 cytokine release. Terminal cell lysis and IL-1β release following caspase activation can be uncoupled in certain cell types or in response to particular stimuli, a state termed hyperactivation. However, the factors and mechanisms that regulate terminal cell lysis downstream of GSDMD cleavage remain poorly understood. In the course of studies to define regulation of pyroptosis during Yersinia infection, we identified a line of Card19-deficient mice (Card19lxcn) whose macrophages were protected from cell lysis and showed reduced apoptosis and pyroptosis, yet had wPLoS pathogensGenetic targeting of Card19 is linked to disrupted NINJ1 expression, impaired cell lysis, and increased susceptibility to Yersinia infection.PMC8547626PATHR01 AI128530R01HL136572AI125924Chang Zuckerberg Initiative AwardR21 AI125924AI128530PEW Biomedical Scholars awardR01 AI139102R01AI125552R21 AI135421R01 HL136572R01 AI125552Kornfeld OSChen KWMatsuda RDeLaney AARodriguez Lopez EMPhilip NHBjanes EDemarco BJoannas LSillas RGHenao-Mejia JKrespan ETovar DBroz PBrodsky IEFettrelet TLee BLSchaefer BCGrubaugh DWynosky-Dolfi MABeiting DPfalseGenetic targeting of Card19 is linked to disrupted NINJ1 expression, impaired cell lysis, and increased susceptibility to Yersinia infection.Cell death plays a critical role in inflammatory responses. During pyroptosis, inflammatory caspases cleave Gasdermin D (GSDMD) to release an N-terminal fragment that generates plasma membrane pores that mediate cell lysis and IL-1 cytokine release. Terminal cell lysis and IL-1β release following caspase activation can be uncoupled in certain cell types or in response to particular stimuli, a state termed hyperactivation. However, the factors and mechanisms that regulate terminal cell lysis downstream of GSDMD cleavage remain poorly understood. In the course of studies to define regulation of pyroptosis during Yersinia infection, we identified a line of Card19-deficient mice (Card19lxcn) whose macrophages were protected from cell lysis and showed reduced apoptosis and pyroptosis, yet had w2021-01-01T00:00:00Z2021 Oct2026-05-08T16:08:35.652Z2024-10-15T09:45:08.699ZS-EPMC85476263464859010.1371/journal.ppat.1009967