Pathogenic <i>Vibrio</i> Activate NLRP3 Inflammasome via Cytotoxins and TLR/Nucleotide-Binding Oligomerization Domain-Mediated NF-κB Signaling

Toma, Claudia; Higa, Naomi; Koizumi, Yukiko; Nakasone, Noboru; Ogura, Yasunori; McCoy, Andrea J.; Franchi, Luigi; Uematsu, Satoshi; Sagara, Junji; Taniguchi, Shun’ichiro; Tsutsui, Hiroko; Akira, Shizuo; Tschopp, Jürg; Núñez, Gabriel; Suzuki, Toshihiko

doi:10.4049/jimmunol.0903536

Cited by 134 publications

(145 citation statements)

References 74 publications

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“…This is in contrast to previously published studies with mouse macrophages that had, in addition to hemolysin, linked inflammasome activation to CTB (18,22) and the MARTX toxin (17).…”

Section: Resultscontrasting

confidence: 99%

“…To assess if the accessory toxins account for inflammasome activation in THP-1 cells, as previously shown in murine macrophages (17), V. cholerae P4 (El Tor P27459⌬ctxAB) was confirmed to produce the accessory toxins by its abilities to induce covalent cross-linking of actin in THP-1 cells dependent on the MARTX toxin encoded by the rtxA gene ( Fig. 2A) and to secrete hemolysin dependent upon the hemolysin gene hlyA ( When incubated with THP-1 cells, ⌬ctxAB mutant strain P4 induced IL-1␤ secretion dependent upon ASC, and additional deletion of the hlyA gene completely abolished ASC-dependent IL-1␤ secretion (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The pore-forming hemolysin is known to induce the activation of IL-1␤ from murine macrophages via the cytosolic PRR NLRP3 (17). To test if hemolysin-stimulated IL-1␤ production in THP-1 cells is also due to NLRP3, we tested NLRP3def THP-1 cells.…”

Section: Resultsmentioning

confidence: 99%

“…In particular, numerous studies have shown a linkage between V. cholerae activation of the inflammasome in innate immune cells resulting in release of the proinflammatory cytokine IL-1␤ (17,18,20,31). Both V. cholerae and purified secreted components of V. cholerae have been examined recently as activators of noncanonical inflammasomes (18,20), wherein CTB is found to function as a carrier of E. coli O111:B4 LPS into the cytosol to stimulate caspase-11 (22).…”

Section: Discussionmentioning

confidence: 99%

“…These cytokines, in turn, recruit monocytes, macrophages, and neutrophils to the site of infection and induce Th1 and Th17 adaptive immunity (15,16). The V. cholerae accessory toxins hemolysin and the MARTX toxin have both been shown to activate the NLRP3 inflammasome in murine macrophages, resulting in the processing and secretion of IL-1␤ (17).…”

mentioning

confidence: 99%

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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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“…This is in contrast to previously published studies with mouse macrophages that had, in addition to hemolysin, linked inflammasome activation to CTB (18,22) and the MARTX toxin (17).…”

Section: Resultscontrasting

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

et al. 2015

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Caspase‐11: The driving factor for noncanonical inflammasomes

Viganò

Mortellaro

2013

Eur J Immunol

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Inflammasomes are large multiprotein platforms that mediate the processing of caspase-1, which in turn promotes the maturation and release of IL-1β and IL-18 in response to microbial and danger signals. While the canonical pathway of inflammasome activation has been known for some time, a novel mechanism of noncanonical inflammasome activation mediated by caspase-11 was more recently identified. This pathway engages caspase-11 to trigger both caspase-1-dependent and -independent production of the inflammatory cytokines IL-1β, IL-18, and IL-1α, as well as to promote pyroptosis, a form of genetically programmed cell death that is associated with the release of such cytokines. In this review, we gather together studies on both the mechanisms and implications of caspase-11-mediated noncanonical inflammasome activation, and discuss the emerging importance of this pathway in regulating host defense against intracellular bacterial pathogens.

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An overview of programmed cell death: Apoptosis and pyroptosis—Mechanisms, differences, and significance in organism physiology and pathophysiology

Kowalski,

Karska,

Łapińska

et al. 2023

J of Cellular Biochemistry

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Regulated cell death is an essential and heterogeneous process occurring in the life cycle of organisms, from embryonic development and aging to the regulation of homeostasis and organ maintenance. Under this term, we can distinguish many distinct pathways, including apoptosis and pyroptosis. Recently, there has been an increasing comprehension of the mechanisms governing these phenomena and their characteristic features. The coexistence of different types of cell death and the differences and similarities between them has been the subject of many studies. This review aims to present the latest literature in the field of pyroptosis and apoptosis and compare their molecular pathway's elements and significance in the physiology and pathophysiology of the organism.

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Pathogenic Vibrio Activate NLRP3 Inflammasome via Cytotoxins and TLR/Nucleotide-Binding Oligomerization Domain-Mediated NF-κB Signaling

Cited by 134 publications

References 74 publications

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

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

Caspase‐11: The driving factor for noncanonical inflammasomes

An overview of programmed cell death: Apoptosis and pyroptosis—Mechanisms, differences, and significance in organism physiology and pathophysiology

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