Caspase‐1‐dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages

By S. Fink, B. Cookson. Cellular Microbiology, 2006

1,100 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e91642a38aac8d9c7df55397028d54dd9eb4fad8

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In Epidemiology

1. Taro Kawai
2. T. Kanneganti
3. Edward A. Miao
4. B. Cookson
5. S. Fink
6. Himanshu Kumar
7. G. Núñez
8. V. Dixit

In Molecular Biology

1. T. Kanneganti
2. Edward A. Miao
3. V. Dixit
4. G. Núñez
5. F. Shao
6. R. Malireddi
7. S. Kesavardhana
8. Shizuo Akira

Citations in the corpus

• The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation (2007, result): “In this report, we addressed the role of the adapter protein ASC in the inflammatory cell death that has been recently termed pyroptosis.(23,24) Although pyroptosis was first recognized in cells infected with intracellular pathogens, our results show that non-infectious agents like LPS, R837, MSU, S”
• NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation and fibrosis (2014, background): “However, in contrast to apoptosis, pyroptosis is also associated with cell swelling, the release of proinflammatory intracellular contents, and pore formation in the cell membrane, thereby becoming positive for propidium iodide (PI) staining.(13,14) We, and others, have recently shown that hepatic C”
• The pore forming protein gasdermin D regulates interleukin-1 secretion from living macrophages (2017, neutral): “To determine whether GSDMD influences IL-1 release from intact cells, we utilized the osmoprotectant glycine to prevent pyroptosis-associated membrane rupture (Fink and Cookson, 2006).”
• Pathogen Recognition by the Innate Immune System (2011, background): “The NLRC4 inflammasome is mainly composed of CARD-containing NLRC4 [122] (also known as IPAF) and procaspase-1, and is activated via direct interaction with the CARDs of caspase-1 and NLRC4 to induce pyroptosis through caspase-1 activation [123].”
• GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes (2016, background): “by formation of pores in the plasma membrane (13, 14), that ectopic GsdmD p30 kills cells (8, 9), and that the C-terminal domain of another gasdermin family member inhibits toxicity of the corresponding N-terminal domain (15), our observations argue that GsdmD p30 that is liberated by caspase-11 for”
• Pyroptosis in inflammatory diseases and cancer (2022, background): “The factors released during cell death, such as interleukin-1β (IL-1β) and interleukin-18 (IL-18), amplify the inflammatory effects and activate immune responses [6, 7].”
• Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death. (2017, background): “typhimurium-infected macrophages but are not required for cell death [75].”
• Pyroptotic cell death defends against intracellular pathogens (2015, background): “Following permabilization of the plasma membrane, ions and water rush into the cell causing it to swell and lyse, resulting in the release of cytosolic contents (3).”
• Caspases in Cell Death, Inflammation, and Gasdermin-Induced Pyroptosis (2020, background): “Although pyroptosis has long been considered a monocytic cell death pathway driven by caspase-1, it was later identified that caspase-4, -5, and -11 also drive pyroptosis efficiently, but are ineffective in direct cytokine processing (3, 104, 107, 109, 110) (Figure 1).”
• Pyroptosis: host cell death and inflammation (2009, background): “However, caspase 1 activation can result not only in the production of activated inflammatory cytokines, but also rapid cell death characterized by plasma-membrane rupture and release of proinflammatory intracellular content”
• The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation (2016, background): “Similar to Inflammasome activation and regulation • Sharma and Kanneganti 623 necrosis, pyroptosis involves the formation of 1- to 2-nm pores on the cell membrane (Fink and Cookson, 2006).”