Activation of inflammasomes requires intracellular redistribution of the apoptotic speck-like protein containing a caspase recruitment domain

Nicole B. Bryan, Andrea Dorfleutner, Yon Rojanasakul, Christian Stehlik*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

Activation of caspase 1 is essential for the maturation and release of IL-1β and IL-18 and occurs in multiprotein complexes, referred to as inflammasomes. The apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is the essential adaptor protein for recruiting pro-caspase 1 into inflammasomes, and consistently gene ablation of ASC abolishes caspase 1 activation and secretion of IL-1β and IL-18. However, distribution of endogenous ASC has not yet been examined in detail. In the present study, we demonstrated that ASC localized primarily to the nucleus in resting human monocytes/macrophages. Upon pathogen infection, ASC rapidly redistributed to the cytosol, followed by assembly of perinuclear aggregates, containing several inflammasome components, including caspase 1 and Nod-like receptors. Prevention of ASC cytosolic redistribution completely abolished pathogen-induced inflammasome activity, which affirmed that cytosolic localization of ASC is essential for inflammasome function. Thus, our study characterized a novel mechanism of inflammasome regulation in host defense.

Original languageEnglish (US)
Pages (from-to)3173-3182
Number of pages10
JournalJournal of Immunology
Volume182
Issue number5
DOIs
StatePublished - Mar 1 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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