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Review
. 2015 May;265(1):130-42.
doi: 10.1111/imr.12287.

Pyroptotic cell death defends against intracellular pathogens

Ine Jorgensen  1 , Edward A Miao
Affiliations
Review

Pyroptotic cell death defends against intracellular pathogens

Ine Jorgensen et al. Immunol Rev. 2015 May.

Abstract

Inflammatory caspases play a central role in innate immunity by responding to cytosolic signals and initiating a twofold response. First, caspase-1 induces the activation and secretion of the two prominent pro-inflammatory cytokines, interleukin-1β (IL-1β) and IL-18. Second, either caspase-1 or caspase-11 can trigger a form of lytic, programmed cell death called pyroptosis. Pyroptosis operates to remove the replication niche of intracellular pathogens, making them susceptible to phagocytosis and killing by a secondary phagocyte. However, aberrant, systemic activation of pyroptosis in vivo may contribute to sepsis. Emphasizing the efficiency of inflammasome detection of microbial infections, many pathogens have evolved to avoid or subvert pyroptosis. This review focuses on molecular and morphological characteristics of pyroptosis and the individual inflammasomes and their contribution to defense against infection in mice and humans.

Keywords: caspase-1; caspase-11; inflammasome; inflammatory caspases; pyroptosis.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1. Activation of inflammatory caspases by canonical and non-canonical inflammasomes
Caspase-1 is activated by several inflammasomes, which are multi-protein signaling complexes that assemble in response the detection of cellular perturbations or intracellular microbial ligands. The currently known inflammasomes are encompassed within three gene families: Nod-like receptors (NLRs), AIM2-like receptors (ALRs), or tripartite motif family (TRIM) (of which only one member is an inflammasome: Pyrin). The noncanonical inflammasomes consists of caspase-11, which directly senses LPS. Activation of both the canonical and noncanonical inflammasome induces pyroptosis and the secretion of the pro-inflammatory cytokines IL-1β and IL-18. For CARD-containing inflammasomes, pyroptosis and cytokine secretion occurs independently and dependently of ASC, respectively, with the exception of NLRP1, which does not require ASC for cytokine secretion. Caspase-11 induces cytokine secretion via NLRP3/ASC by an unknown mechanism.
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