Critical Role for Cryopyrin/Nalp3 in Activation of Caspase-1 in Response to Viral Infection and Double-stranded RNA*>

By T. Kanneganti, Mathilde Body-Malapel, A. Amer, Jong-Hwan Park, J. Whitfield, L. Franchi, Z. Taraporewala, David Miller, J. Patton, N. Inohara and 1 more. Journal of Biological Chemistry, 2006

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Viral infection induces the production of interleukin (IL)-1β and IL-18 in macrophages through the activation of caspase-1, but the mechanism by which host cells sense viruses to induce caspase-1 activation is unknown. In this report, we have identified a signaling pathway leading to caspase-1 activation that is induced by double-stranded RNA (dsRNA) and viral infection that is mediated by Cryopyrin/Nalp3. Stimulation of macrophages with dsRNA, viral RNA, or its analog poly(I:C) induced the secretion of IL-1β and IL-18 in a cryopyrin-dependent manner. Consistently, caspase-1 activation triggered by poly(I:C), dsRNA, and viral RNA was abrogated in macrophages lacking cryopyrin or the adaptor ASC (apoptosis-associated speck-like protein containing a caspase-activating and recruitment domain) but proceeded normally in macrophages deficient in Toll-like receptor 3 or 7. We have also shown that infection with Sendai and influenza viruses activates the cryopyrin inflammasome. Finally, cryopyrin was required for IL-1β production in response to poly(I:C) in vivo. These results identify a mechanism mediated by cryopyrin and ASC that links dsRNA and viral infection to caspase-1 activation resulting in IL-1β and IL-18 production.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/b3cd4c8be5931a8b01a8e8d6962936f3668b1450

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Citations in the corpus

Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration (2007, background): “For example, bacterial muramyl dipeptide (MDP),(15) a degradation product of the bacterial cell wall component peptidoglycans (PGN), as well as RNA of bacterial and viral origin activate NALP3.(16,17) Besides these classical PAMPs, the microbial toxins nigericin (Streptomyces hygroscopicus), aerolys”
Caspase functions in cell death and disease. (2013, background): “Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA.”
ZBP1 and TAK1: Master Regulators of NLRP3 Inflammasome/Pyroptosis, Apoptosis, and Necroptosis (PAN-optosis) (2019, background): “…family pyrin domain-containing 3 (NLRP3) in sensing IAV infection and dsRNAs to assemble the inflammasome complex via the adapter protein apoptosisassociated speck-like protein containing a caspase recruitment domain (ASC) and drive caspase-1–mediated inflammation (Kanneganti et al., 2006a,b).”
NLRP3 (NALP3/CIAS1/Cryopyrin) mediates key innate and healing responses to influenza A virus via the regulation of caspase-1 (2009, positive): “Recently, we and others reported that both cytosolic poly(I:C) and viral RNA induce caspase-1 activation and the subsequent processing and secretion of IL-1b and IL-18 in vitro via a Cryopyrin-dependent pathway (Kanneganti et al., 2006; Pirhonen et al., 2001; Pirhonen et al., 1999).”
The inflammasomes. (2010, neutral): “The notion that innate immunity functions as a danger sentinel has similarities to Matzinger’s ‘‘danger hypothesis,’’ proposed for adaptive immune responses (Matzinger, 1994).”
Pyroptosis: host cell death and inflammation (2009, background): “, extracellular ATP in the presence of various pathogen-associated molecule”
The NLRP3 inflammasome protects against loss of epithelial integrity and mortality during experimental colitis (2010, positive): “Hence, mice lacking caspase-1 are defective in the maturation and secretion of IL-1b and IL-18 (Ghayur et al., 1997; Kuida et al., 1995; Li et al., 1995).”
Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses (2009, background): “ascribed a role in recognition of ATP (226), uric acid crystals (232), viral RNA (168), and bacterial DNA (268), whereas”
Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β–dependent adaptive immunity against tumors (2009, background): “Multiple distinct bacterial products or endogenous damage signals stimulate the NLRP3 inflammasome, resulting in the proteolytic activation of caspase-”
Cooperation of Toll-like receptor signals in innate immune defence (2007, background): “In addition, ASC- and NALP3-deficient mice have an impaired contact hypersensitivity response to the hapten trinitrophenylchloride and have decreased secretion of IL-1β and IL-18 when cultured with the Gram-positive bacteria Staphylococcus aureus and Listeria monocytogenes”
Inflammasomes and their roles in health and disease. (2012, background): “Consequently, ASC is essential for assembly and activation of these PYD-containing inflammasomes (Agostini et al. 2004, Elinav et al. 2011, Kanneganti et al. 2006, Mariathasan et al. 2006, Sutterwala et al. 2006).”
Type I interferon inhibits interleukin-1 production and inflammasome activation. (2011, background): “Moreover, viral RNA and poly(I:C) were reported to induce release of IL-1b through activation of the NLRP3 inflammasome (Allen et al., 2009; Kanneganti et al., 2006).”