The NLR Gene Family: A Standard Nomenclature

Ting, Jenny P.-Y.; Lovering, Ruth C.; Alnemri, Emad S.; Bertin, John; Boss, Jeremy M.; Davis, Beckley K.; Flavell, Richard A.; Girardin, Stephen E.; Godzik, Adam; Harton, Jonathan A.; Hoffman, Hal M.; Hugot, Jean‐Pierre; Inohara, Naohiro; MacKenzie, Alex; Maltais, Lois J.; Núñez, Gabriel; Ogura, Yasunori; Otten, L.; Philpott, Dana J.; Reed, John C.; Reith, Walter; Schreiber, Stefan; Steimle, Viktor; Ward, Peter A.

doi:10.1016/j.immuni.2008.02.005

Cited by 788 publications

(599 citation statements)

References 43 publications

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“…These POPs are not present in mouse cells (45). In addition, human and mouse macrophages differ in the expression of NLR and ALR genes (27,46). Thus, the difference in the system may reflect actual variation in the signaling of inflammasome activation, but this will need to be examined further.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…Tous possèdent une structure organisée en domaines [5]. À l'instar des TLR, l'extrémité carboxy-terminale comporte un domaine leucine-rich repeats (LRR) composé d'une répétition caractéristique de 20 à 30 acides aminés, riche en leucine.…”

Section: Les Récepteurs Nlrunclassified

“…L'extrémité amino-terminale porte le domaine effecteur des NLR, responsable de la transduction du signal. La nouvelle nomenclature des NLR les regroupe en sous-familles en fonction du domaine effecteur [5] [13]. Depuis la découverte pionnière de l'inflammasome NLRP1, le nombre de récepteurs se comportant comme des activateurs de la caspase-1 n'a cessé d'augmenter.…”

Section: Les Récepteurs Nlrunclassified

Les inflammasomes

Jamilloux

Henry

2013

Med Sci (Paris)

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“…5) [141]. NLRPs contain PYD, while CARD mediates downstream protein-protein interaction in NLRCs [142]. Recently, AIM2, a non-NLR family member belonging to the interferon-inducible HIN-200 protein family, was identified as a cytosolic double-stranded DNA (dsDNA) sensor facilitating formation of the AIM2 inflammasome.…”

Section: The Inflammasome-mediated Pathwaymentioning

confidence: 99%

Muramyl dipeptide responsive pathways in Crohn’s disease: from NOD2 and beyond

Salem

Seidelin

Rogler

et al. 2012

Cell. Mol. Life Sci.

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Crohn's disease (CD) is one of main disease entities under the umbrella term chronic inflammatory bowel disease. The etiology of CD involves alterations in genetic, microbiological, and immunological factors. This review is devoted to the role of the bacterial wall compound muramyl dipeptide (MDP) for the activation of inflammatory pathways involved in the pathogenesis of CD. The importance of this molecule is underscored by the fact that (1) MDP, which is found in most Gram-negative and -positive bacteria, is able to trigger several immunological responses in the intestinal system, and (2) that alterations in several mediators of the MDP response including-but not restricted to-nucleotide oligomerization domain 2 (NOD2) are associated with CD. The normalization of MDP signaling is one of several important factors that influence the intestinal inflammatory response, a fact which emphasizes the pathogenic importance of MDP signaling for the pathogenesis of CD. The important aspects of NOD2 and non-NOD2 mediated effects of MDP for the development of CD are highlighted, as well as how alterations in these pathways might translate into the development of new therapeutic strategies.

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The NLR Gene Family: A Standard Nomenclature

Cited by 788 publications

References 43 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

Les inflammasomes

Muramyl dipeptide responsive pathways in Crohn’s disease: from NOD2 and beyond

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