Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages.
Susan L. Fink,Brad T. Cookson +1 more
TLDR
This mechanism of caspase‐1‐mediated cell death provides additional experimental evidence supporting pyroptosis as a novel pathway of inflammatory programmed cell death.Abstract:
Salmonella enterica serovar Typhimurium invades host macrophages and induces a unique caspase-1-dependent pathway of cell death termed pyroptosis, which is activated during bacterial infection in vivo. We demonstrate DNA cleavage during pyroptosis results from caspase-1-stimulated nuclease activity. Although poly(ADP-ribose) polymerase (PARP) activation by fragmented DNA depletes cellular ATP to cause lysis during oncosis, the rapid lysis characteristic of Salmonella-infected macrophages does not require PARP activity or DNA fragmentation. Membrane pores between 1.1 and 2.4 nm in diameter form during pyroptosis of host cells and cause swelling and osmotic lysis. Pore formation requires host cell actin cytoskeleton rearrangements and caspase-1 activity, as well as the bacterial type III secretion system (TTSS); however, insertion of functional TTSS translocons into the host membrane is not sufficient to directly evoke pore formation. Concurrent with pore formation, inflammatory cytokines are released from infected macrophages. This mechanism of caspase-1-mediated cell death provides additional experimental evidence supporting pyroptosis as a novel pathway of inflammatory programmed cell death.read more
Citations
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What role does pyroptosis play in microbial infection
TL;DR: The role of pyroptosis in microbial infection-related diseases is discussed in this article, where a review of the molecular mechanisms of pyroposis and its role in the development of various diseases caused by microbial infection is presented.
Journal ArticleDOI
Group 2 innate lymphoid cells protect lung endothelial cells from pyroptosis in sepsis
Dengming Lai,Jing Tang,Linsong Chen,Linsong Chen,Erica K. Fan,Melanie J. Scott,Yuehua Li,Yuehua Li,Timothy R. Billiar,Mark Wilson,Mark Wilson,Xiangming Fang,Qiang Shu,Jie Fan,Jie Fan +14 more
TL;DR: It is shown that the increased ILC2 in the lungs secrete IL-9, which in turn prevents lung EC from undergoing pyroptosis, a pro-inflammatory cell death form, by attenuating caspase-1 activation, suggesting a previously unidentified innate pathway that negatively regulates lung inflammation following sepsis.
Journal ArticleDOI
Catching fire: Candida albicans, macrophages, and pyroptosis.
TL;DR: The understanding of the mechanisms and consequences of the interaction between macrophages and C. albicans is improving, but much remains to be learned.
Journal ArticleDOI
Dependency of caspase-1 activation induced in macrophages by Listeria monocytogenes on cytolysin, listeriolysin O, after evasion from phagosome into the cytoplasm.
TL;DR: Results show that the LLO molecule is involved in the activation of caspase-1, which is essential for IL-18 production in infected macrophages, and suggest that some sequence unique to LLO is indispensable for some signaling event resulting in the caspasing-1 activation induced by L. monocytogenes.
Journal ArticleDOI
Structure, Activation and Regulation of NLRP3 and AIM2 Inflammasomes.
Meenakshi Sharma,Eva de Alba +1 more
TL;DR: The inflammasome is a three-component (sensor, adaptor, and effector) filamentous signaling platform that shields from multiple pathogenic infections by stimulating the proteolytical maturation of proinflammatory cytokines and pyroptotic cell death as mentioned in this paper.
References
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Journal ArticleDOI
Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells
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