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dc.contributor.authorZhong, Q
dc.contributor.authorRoumeliotis, TI
dc.contributor.authorKozik, Z
dc.contributor.authorCepeda-Molero, M
dc.contributor.authorFernández, LÁ
dc.contributor.authorShenoy, AR
dc.contributor.authorBakal, C
dc.contributor.authorFrankel, G
dc.contributor.authorChoudhary, JS
dc.date.accessioned2021-01-22T15:30:16Z
dc.date.issued2020-12-30
dc.identifier.citationPLoS biology, 2020, 18 (12), pp. e3000986 - ?
dc.identifier.issn1544-9173
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4307
dc.identifier.eissn1545-7885en_US
dc.identifier.doi10.1371/journal.pbio.3000986en_US
dc.description.abstractClustering of the enteropathogenic Escherichia coli (EPEC) type III secretion system (T3SS) effector translocated intimin receptor (Tir) by intimin leads to actin polymerisation and pyroptotic cell death in macrophages. The effect of Tir clustering on the viability of EPEC-infected intestinal epithelial cells (IECs) is unknown. We show that EPEC induces pyroptosis in IECs in a Tir-dependent but actin polymerisation-independent manner, which was enhanced by priming with interferon gamma (IFNγ). Mechanistically, Tir clustering triggers rapid Ca2+ influx, which induces lipopolysaccharide (LPS) internalisation, followed by activation of caspase-4 and pyroptosis. Knockdown of caspase-4 or gasdermin D (GSDMD), translocation of NleF, which blocks caspase-4 or chelation of extracellular Ca2+, inhibited EPEC-induced cell death. IEC lines with low endogenous abundance of GSDMD were resistant to Tir-induced cell death. Conversely, ATP-induced extracellular Ca2+ influx enhanced cell death, which confirmed the key regulatory role of Ca2+ in EPEC-induced pyroptosis. We reveal a novel mechanism through which infection with an extracellular pathogen leads to pyroptosis in IECs.
dc.formatElectronic-eCollection
dc.format.extente3000986 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleClustering of Tir during enteropathogenic E. coli infection triggers calcium influx-dependent pyroptosis in intestinal epithelial cells.
dc.typeJournal Article
dcterms.dateAccepted2020-11-24
rioxxterms.versionofrecord10.1371/journal.pbio.3000986
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-12-30en_US
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfPLoS biology
pubs.issue12
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Dynamical Cell Systems
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Dynamical Cell Systems
pubs.publication-statusPublished
pubs.volume18en_US
pubs.embargo.termsNot known
icr.researchteamDynamical Cell Systemsen_US
dc.contributor.icrauthorBakal, Christopheren
dc.contributor.icrauthorRoumeliotis, Theodorosen
dc.contributor.icrauthorChoudhary, Jyotien


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