TRIF Licenses Caspase-11-Dependent NLRP3 Inflammasome Activation by Gram-Negative Bacteria

Rathinam, Vijay; Vanaja, Sivapriya Kailasan; Waggoner, Lisa; Sokolovska, Anna; Becker, Christine; Stuart, Lynda M.; Leong, John M.; Fitzgerald, Katherine A.

doi:10.1016/j.cell.2012.07.007

Cited by 636 publications

(774 citation statements)

References 46 publications

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“…3). Caspase-11 protein is either auto-activated or activated by unknown receptors that are induced by endogenous Type I IFNs (Broz et al 2012;Rathinam et al 2012). In addition, LPS from E. coli O111:B4 is found to bind CTB and the LPS-CTB conjugate is engulfed by bone marrow-derived M/.…”

Section: Caspase-11mentioning

confidence: 99%

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Caspases as the Key Effectors of Inflammatory Responses Against Bacterial Infection

Uchiyama

Tsutsui

2014

Arch. Immunol. Ther. Exp.

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Section: Caspase-11mentioning

confidence: 99%

“…The production of IL-1b/IL-18 is regulated by Type I IFNs (Guarda et al 2011;Rathinam et al 2012). In addition, L. monocytogenes infections induce the expression of Type I IFNs including IFN-b (Reimer et al 2007;Reutterer et al 2008;Yamamoto et al 2012).…”

Section: Caspase-8 Activation and Il-1b/il-18 Processing Through Fasmentioning

confidence: 99%

Caspases as the Key Effectors of Inflammatory Responses Against Bacterial Infection

Uchiyama

Tsutsui

2014

Arch. Immunol. Ther. Exp.

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“…Noncanonical activation of IL-1␤ in mouse macrophages is primed by Toll-like receptor 4 (TLR4)-TRIF-IFNAR and activated by cytosolic lipopolysaccharide (LPS) binding caspase-11 in mice and caspase-4/5 in humans (18)(19)(20)(21)(22)(23). Secreted CTB has been shown to act as a carrier of O111:B4 LPS into the cytosol, leading to activation of caspase-11 and resulting in IL-1␤ release (18,22).…”

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confidence: 99%

Mechanisms of Inflammasome Activation by Vibrio cholerae Secreted Toxins Vary with Strain Biotype

et al. 2015

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Activation of inflammasomes is an important aspect of innate immune responses to bacterial infection. Recent studies have linked Vibrio cholerae secreted toxins to inflammasome activation by using murine macrophages. To increase relevance to human infection, studies of inflammasome-dependent cytokine secretion were conducted with the human THP-1 monocytic cell line and corroborated in primary human peripheral blood mononuclear cells (PBMCs). Both El Tor and classical strains of V. cholerae activated ASC (apoptosis-associated speck-like protein-containing a CARD domain)-dependent release of interleukin-1␤ (IL-1␤) when cultured with human THP-1 cells, but the pattern of induction was distinct, depending on the repertoire of toxins the strains produced. El Tor biotype strains induced release of IL-1␤ dependent on NOD-like receptor family pyrin domain-containing 3 (NLRP3) and ASC due to the secreted pore-forming toxin hemolysin. Unlike in studies with mouse macrophages, the MARTX toxin did not contribute to IL-1␤ release from human monocytic cells. Classical biotype strains, which do not produce either hemolysin or the MARTX toxin, activated low-level IL-1␤ release that was induced by cholera toxin (CT) and dependent on ASC but independent of NLRP3 and pyroptosis. El Tor strains likewise showed increased IL-1␤ production dependent on CT when the hemolysin gene was deleted. In contrast to studies with murine macrophages, this phenotype was dependent on a catalytically active CT A subunit capable of inducing production of cyclic AMP and not on the B subunit. These studies demonstrate that the induction of the inflammasome in human THP-1 monocytes and in PBMCs by V. cholerae varies with the biotype and is mediated by both NLRP3-dependent and -independent pathways. V ibrio cholerae is the causative agent of the diarrheal disease cholera. The O1 serogroup, which is most associated with disease, is divided into two biotypes, classical and El Tor. Classical strains were responsible for the six cholera pandemics that occurred during the 19th century and the first half of the 20th century and are noted for their severe clinical presentation. In 1961, the El Tor strains emerged as the cause of the ongoing seventh pandemic, completely displacing the classical strains from the environment and as a cause of cholera in humans (1). These strains colonize the intestine more effectively and spread between hosts more efficiently but cause fewer deaths and significantly more asymptomatic colonization (2).The primary virulence factor for pandemic cholera strains is cholera toxin (CT), an ADP-ribosylating toxin that disables the G␣ s subunit, resulting in increased cyclic AMP (cAMP) production and secretion of fluid from enterocytes due to the opening of chloride channels. The toxin is composed of the catalytically active A (CTA) subunit associated with five CTB subunits that bind to surface GM 1 gangliosides, facilitating toxin endocytosis (3). In addition to enterotoxigenic activity, CT has also been demonstrated to have immunomodulat...

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“…Like caspase-1, active caspase-11 triggers pyroptosis. Surprisingly, caspase-11 appears unable to directly cleave cytokines, and only does so indirectly through an unresolved mechanism involving NLRP3 and caspase-1 [19]. Recent studies suggest that caspase-11 is activated through a surprising mechanism involving direct interaction between the pro-caspase-11 CARD domain and LPS, triggering caspase dimerisation and activation, within the so-called 'non-canonical inflammasome' complex [20].…”

Section: Pyroptosis Initiation By Other Inflammatory Caspasesmentioning

confidence: 99%

Burn the house, save the day: pyroptosis in pathogen restriction

Boucher¹,

Chen²,

Schroder³

2016

Inflammasome

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Many programmed cell death pathways are essential for organogenesis, development, immunity and the maintenance of homeostasis in multicellular organisms. Pyroptosis, a highly proinflammatory form of cell death, is a critical innate immune response to prevent intracellular infection. Pyroptosis is induced upon the activation of proinflammatory caspases within macromolecular signalling platforms called inflammasomes. This article reviews our understanding of pyroptosis induction, the function of inflammatory caspases in pyroptosis execution, and the importance of pyroptosis for pathogen clearance. It also highlights the situations in which extensive pyroptosis may in fact be detrimental to the host, leading to immune cell depletion or cytokine storm. Current efforts to understand the beneficial and pathological roles of pyroptosis bring the promise of new approaches to fight infectious diseases.

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TRIF Licenses Caspase-11-Dependent NLRP3 Inflammasome Activation by Gram-Negative Bacteria

Cited by 636 publications

References 46 publications

Caspases as the Key Effectors of Inflammatory Responses Against Bacterial Infection

Caspases as the Key Effectors of Inflammatory Responses Against Bacterial Infection

Mechanisms of Inflammasome Activation by Vibrio cholerae Secreted Toxins Vary with Strain Biotype

Burn the house, save the day: pyroptosis in pathogen restriction

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