Coordinated host responses during pyroptosis: Caspase-1-dependent lysosome exocytosis and inflammatory cytokine maturation

Tessa Bergsbaken, Susan L. Fink, Andreas B. Den Hartigh, Wendy P. Loomis, Brad T. Cookson

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Activation of caspase-1 leads to pyroptosis, a program of cell death characterized by cell lysis and inflammatory cytokine release. Caspase-1 activation triggered by multiple nucleotide-binding oligomerization domain-like receptors (NLRs; NLRC4, NLRP1b, or NLRP3) leads to loss of lysosomes via their fusion with the cell surface, or lysosome exocytosis. Active caspase-1 increased cellular membrane permeability and intracellular calcium levels, which facilitated lysosome exocytosis and release of host antimicrobial factors and microbial products. Lysosome exocytosis has been proposed to mediate secretion of IL-1β and IL-18; however, blocking lysosome exocytosis did not alter cytokine processing or release. These studies indicate two conserved secretion pathways are initiated by caspase-1, lysosome exocytosis, and a parallel pathway resulting in cytokine release, and both enhance the antimicrobial nature of pyroptosis. Copyright

Original languageEnglish (US)
Pages (from-to)2748-2754
Number of pages7
JournalJournal of Immunology
Volume187
Issue number5
DOIs
StatePublished - Sep 1 2011
Externally publishedYes

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this