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

T Bergsbaken, SL Fink, AB Den Hartigh… - The Journal of …, 2011 - journals.aai.org
T Bergsbaken, SL Fink, AB Den Hartigh, WP Loomis, BT Cookson
The Journal of Immunology, 2011journals.aai.org
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 …
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.
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