Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria

By Edward A. Miao, I. Leaf, P. Treuting, Dat P. Mao, Monica Dors, A. Sarkar, S. Warren, M. Wewers, Alan Aderem. Nature Immunology, 2010

1,280 citations recorded by the source corpus.

Macrophages mediate crucial innate immune responses via caspase-1-dependent processing and secretion of interleukin 1β (IL-1β) and IL-18. Although infection with wild-type Salmonella typhimurium is lethal to mice, we show here that a strain that persistently expresses flagellin was cleared by the cytosolic flagellin-detection pathway through the activation of caspase-1 by the NLRC4 inflammasome; however, this clearance was independent of IL-1β and IL-18. Instead, caspase-1-induced pyroptotic cell death released bacteria from macrophages and exposed the bacteria to uptake and killing by reactive oxygen species in neutrophils. Similarly, activation of caspase-1 cleared unmanipulated Legionella pneumophila and Burkholderia thailandensis by cytokine-independent mechanisms. This demonstrates that activation of caspase-1 clears intracellular bacteria in vivo independently of IL-1β and IL-18 and establishes pyroptosis as an efficient mechanism of bacterial clearance by the innate immune system.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/520d699bc0b8d1163e82d8fa0e1b17fa99515d97

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Citations in the corpus

Caspase-1 induced pyroptotic cell death (2011, background): “In contrast, Burkholderia infection may be controlled primarily via pyroptosis (59).”
Inflammasomes and their roles in health and disease. (2012, background): “The critical role of inflammasome signaling in protection against colon inflammation was confirmed in mice lacking ASC and caspase-1 (Allen et al. 2010, Dupaul-Chicoine et al. 2010, Zaki et al. 2010a) as well as in animals lacking IL-1β and IL-18 or their cognate receptors (Lebeis et al. 2009, Salce”
Human Monocytes Engage an Alternative Inflammasome Pathway. (2016, neutral): “In linewith this, the uncoupling of inflammasome activation and pyroptosis, as seen in alternative inflammasome activation, might enable pro-inflammatory IL-1b signaling while avoiding pyroptosis-associated effector functions (Miao et al., 2010; von Moltke et al., 2012).”
Signaling in innate immunity and inflammation. (2012, background): “” The suicide of infected macrophages by pyroptosis is important for bacterial clearance (Miao et al. 2010), but the critical substrates of caspase-1 in this process still have to be determined.”
NLRP3 inflammasome activation results in hepatocyte pyroptosis, liver inflammation and fibrosis (2014, background): “Casp1-induced pyroptosis in macrophages has been previously shown to be important in intracellular bacteria clearance in vivo independently of IL-1b and IL-18.(26) In addition, Masters et al.”
Mechanisms and functions of inflammasomes. (2014, background): “…components of pathogenic bacteria: flagellin, the building block of their locomotion machinery, and proteins from the type III and IV bacterial secretion systems that inject virulence factors into the host cell (Amer et al., 2006; Franchi et al., 2006; Miao et al., 2006; Miao et al., 2010b).”
Gasdermins: Effectors of pyroptosis (2017, background): “However, since bacteria survive pyroptosis[2,34], the physiologic relevance of bacterial membrane-targeting remains unclear.”
The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation (2019, background): “Pyroptosis forces intracellular pathogens out of their replicative niche, exposing them to other immune factors, and it also triggers cytokine release and the generation of DAMPs to further prepare the immune system to respond to infection [18,19].”
The cell biology of inflammasomes: Mechanisms of inflammasome activation and regulation (2016, background): “…et al., 2008), dendritic cells (Edgeworth et al., 2002), enterocytes (Sellin et al., 2014), and hematopoietic progenitors (Masters et al., 2012), whereas neutrophils and monocytes do not undergo pyroptosis after inflammasome activation (Miao et al., 2010a; Chen et al., 2014; Gaidt et al., 2016).”