TIR, CARD and PYRIN: three domains for an antimicrobial triad

Werts, Catherine; Girardin, Stephen E.; Philpott, Dana J.

doi:10.1038/sj.cdd.4401890

Cited by 139 publications

(106 citation statements)

References 132 publications

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“…Most evidence reported so far argues for a critical role of these proteins in the activation of the NF-jB pathway [3]. In line with this assumption, we recently demonstrated that intraperitoneal injection of FK156 results in a strong and fast Nod1-dependent release of KC [14], the induction of which is mainly driven by NF-jB.…”

Section: Discussionsupporting

confidence: 68%

“…Members of this family also include NALP proteins, IPAF and NAIP, and recent evidence has demonstrated that some NLR serve as intracellular sensors of bacteria and/or danger signals [1][2][3]. The role of Nod1 and Nod2 as intracellular surveillance molecules implicated in the innate immune responses to bacteria has been demonstrated in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…Following detection of their respective peptidoglycan-derived structures, Nod1 and Nod2 engage signaling pathways that are distinct from those triggered by Toll-like receptors (TLR), a family of membrane-anchored PRM. In particular, both Nod1 and Nod2 trigger the recruitment of receptor-interacting protein 2 (also known as RICK or Cardiak), resulting in the activation of NF-jB and JNK/SAPK pathways [3]. For other signaling pathways, such as those implicating p38, ERK or IFN-regulatory factor-3, the ability of Nod1 or Nod2 to induce them has not been studied in detail.…”

Section: Introductionmentioning

confidence: 99%

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Nod1 and Nod2 induce CCL5/RANTES through the NF‐κB pathway

et al. 2007

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The Nod-like receptor proteins Nod1 and Nod2 participate in innate immune responses against bacteria through intracellular detection of peptidoglycan, a component of bacterial cell wall. Recent evidence has demonstrated that Nod1 stimulates the release of chemokines that attract neutrophils at the site of infection, such as CXCL8/IL-8 in humans, and CXCL1/keratinocyte-derived chemokine and CXCL2/MIP-2 in mice. We aimed to determine whether Nod proteins could trigger the release of CCL5/RANTES, a chemokine known to attract a number of immune cells, but not neutrophils. Our results demonstrate that activation of both Nod1 and Nod2 results in substantial secretion of CCL5 by murine macrophages. Moreover, in vivo, the intraperitoneal injection of murine Nod1 or Nod2 agonists resulted in a rapid secretion of CCL5 into the bloodstream. We also observed that Nod-dependent secretion of CCL5 did not correlate with the induction of the interferon-b pathway, a major signaling cascade for the activation of CCL5 by viruses. In contrast, we identified a key role of the NF-jB pathway in Noddependent stimulation of the CCL5 promoter. Together, these results identify a novel target downstream of Nod1 and Nod2, which is likely to play a key role in orchestrating the global Nod-dependent immune defense during bacterial infections.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nod1 and Nod2 induce CCL5/RANTES through the NF‐κB pathway

et al. 2007

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“…These proteins named NOD-like receptors (NLRs) are intracellular sensors of pathogens and other stresses. 53,54 NLRs include proteins such as NOD1 and NOD2, that sense bacterial peptidoglycans and activate the kinase RIP2 and nuclear factor-kB, 55 and three subfamilies of proteins involved in the formation of caspase-1-activating complexes: NALPs, IPAF and NAIPs ( Figure 2). …”

Section: Activation Of Inflammatory Caspases: Inflammasomes and Othermentioning

confidence: 99%

Inflammatory caspases and inflammasomes: master switches of inflammation

2006

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Fifteen years have passed since the cloning and characterization of the interleukin-1b-converting enzyme (ICE/caspase-1), the first identified member of a family of proteases currently known as caspases. Caspase-1 is the prototypical member of a subclass of caspases involved in cytokine maturation termed inflammatory caspases that also include caspase-4 caspase -5, caspase -11 and caspase -12. Efforts to elucidate the molecular mechanisms involved in the activation of these proteases have uncovered an important role for the NLR family members, NALPs, NAIP and IPAF. These proteins promote the assembly of multiprotein complexes termed inflammasomes, which are required for activation of inflammatory caspases. This article will review some evolutionary aspects, biochemical evidences and genetic studies, underlining the role of inflammasomes and inflammatory caspases in innate immunity against pathogens, autoinflammatory syndromes and in the biology of reproduction. Inflammatory CaspasesThe history of caspases began with the identification of an aspartate-specific protease activity involved in the conversion of the 31 kDa proIL-1b precursor to its active 17 kDa biologically active form, 1,2 and the identification of caspase-1 as the protease responsible for proIL-1b maturation. 3,4 The subsequent discovery of ced-3, that shares similarities with caspase-1 and which is involved in programmed cell death (PCD) in Caenorhabditis elegans, suggested that caspases might play fundamental roles in apoptosis. 5 As reviewed in the papers accompanying this issue of Cell Death and Differentiation, the role of apoptotic caspases in C. elegans and in vertebrates is crucial and deal with many facets of cell biology, development and diseases. In this review, we will focus on a subset of caspases present only in vertebrates and known as inflammatory caspases.Inflammatory caspases (also known as group I caspases) are encoded by three main genes in humans caspase-1, caspase-4 and caspase-5 and three main genes in mouse, caspase-1, caspase-11 and caspase-12. 6,7 In mammals, these caspases are characterized by the presence of a CARD domain at the N-terminus (Figure 1a). Human, chimp and mouse inflammatory caspases share significant similarity and are organized in a single locus (Figure 1c). Phylogenetic analysis of the conserved CARD domain suggests that the inflammatory caspases can be separated in evolutionaryrelated clusters (Figure 1b). The caspase-1 cluster contains caspase-1 and four other genes encoding decoy caspases: cop, inca1, inca2 and iceberg. These decoy caspase-1-like genes are absent in the mouse genome, suggesting that they have arisen recently by duplication of caspase-1. Although human and mouse caspase-1 are likely orthologues, sequence analysis suggests that human caspase-4 and caspase-5 have originated from a duplication of caspase-11. 7 However, the human caspase-12 gene, which in the chimp genome contains an SHG box important for it enzymatic activity, 8 evolved towards an enzymatically inactive form at some stage...

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“…Toll-like receptors (TLRs) recognize microbes either on the cell surface or on lysosome/endosome membranes, while pathogens that invade the cytosol are detected by cytoplasmic PRRs, including the Nucleotidebinding Oligomerization Domain-Leucine-Rich Repeat (NOD-LRR) proteins, Peptidoglycan Recognition Proteins (PGRP) and the caspase recruitment domain (CARD)-helicase proteins. [1][2][3][4][5][6] Recent studies suggest that PRRs may also recognize damage-associated molecular pattern molecules (DAMPs) from dying host cells 2 and may induce inflammatory responses in the absence of microbes. Thus, PRRs play a central role in host homeostasis by recognizing both exogenous pathogen-derived and endogenous danger signals.…”

Section: Introduction To Pattern Recognition Receptorsmentioning

confidence: 99%