Nod1 acts as an intracellular receptor to stimulate chemokine production and neutrophil recruitment in vivo

Masumoto, Junya; Yang, Kangkang; Varambally, Sooryanarayana; Hasegawa, Mizuho; Tomlins, Scott A.; Qiu, Su; Fujimoto, Yukari; Kawasaki, Akiko; Foster, Simon J.; Horie, Yasuo; Mak, Tak W.; Núñez, Gabriel; Chinnaiyan, Arul M.; Fukase, Koichi; Inohara, Naohiro

doi:10.1083/jcb1723oia6

Cited by 28 publications

(45 citation statements)

References 41 publications

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“…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. In parallel, through a global microarray analysis of Nod1-induced genes, Masumoto et al [19] have identified that in epithelial cells, the majority of the genes induced by their Nod1 agonist were known to be up-regulated through NF-jB and pro-inflammatory molecules. Interestingly, the authors of this study concluded that the Nod1-dependent induction of KC and MIP-2 participates in the recruitment of neutrophils.…”

Section: Discussionmentioning

confidence: 60%

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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: Discussionmentioning

confidence: 60%

“…Interestingly, IL-8, KC and MIP-2 are chemokines that attract neutrophils at the site of inflammation. In agreement with this assumption, Masumoto et al [19] have recently demonstrated in vivo that intraperitoneal injection of a Nod1-specific agonist results in the recruitment of neutrophils at the injection site.…”

Section: Introductionmentioning

confidence: 59%

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

et al. 2007

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“…MDP (Ac-(6-O-stearoyl)-muramyl-Ala-D-Glu-NH 2 ) was purchased from Bachem. N-myristoyl (C 14 ) ␥-D-glutamyl-meso-diaminopimelic acid (iE-DAP; in a modified form denoted KF1B), a Nod1 activator, has been described (17). The amount of Nod1 and Nod2 stimulatory activity in LPS preparations was determined as described (15,18) and given as units per microgram of weight.…”

Section: Reagents and Bacterial Culturementioning

confidence: 99%

“…To assess the requirement for RICK in TLR4 and Nod1 signaling in vivo, WT and RICK-deficient mice were administered LPS or KF1B, a modified iE-DAP dipeptide and the bacterial activator of Nod1 (17). Injection of LPS i. p. induced comparable levels of KC and IL-6 in WT and RICK-deficient mice (Fig.…”

Section: Differential Requirement Of Rick and Myd88 For Chemokine Andmentioning

confidence: 99%

RICK/RIP2 Mediates Innate Immune Responses Induced through Nod1 and Nod2 but Not TLRs

Park

Kim

McDonald

et al. 2007

The Journal of Immunology

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463

422

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RICK is a kinase that has been implicated in Nod1 and Nod2 signaling. In addition, RICK has been proposed to mediate TLR signaling in that its absence confers reduced responses to certain bacterial products such as LPS. We show here that macrophages and mice lacking RICK are defective in their responses to Nod1 and Nod2 agonists but exhibit unimpaired responses to synthetic and highly purified TLR agonists. Furthermore, production of chemokines induced by the bacterial dipeptide γ-d-glutamyl-meso-diaminopimelic acid was intact in MyD88 deficient mice but abolished in RICK-null mice. Stimulation of macrophages with muramyl dipeptide, the Nod2 activator, enhanced immune responses induced by LPS, IFN-γ, and heat-killed Listeria in wild-type but not in RICK- or Nod2-deficient macrophages. Finally, we show that the absence of RICK or double deficiency of Nod1 and Nod2 was associated with reduced cytokine production in Listeria-infected macrophages. These results demonstrate that RICK functions in innate immunity by mediating Nod1 and Nod2 signaling but not TLR-mediated immune responses.

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“…Ligand binding to NOD-1 or NOD-2 leads to receptor oligomerization, which induces the recruitment of the serine/ threonine kinase Rip2/RICK (Takeda & Akira, 2005). NOD-receptor-bound Rip2/RICK subsequently activates the NF-kB-mediated expression of proinflammatory cytokines (Akira et al, 2006;Masumoto et al, 2006). …”

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confidence: 99%

Exploring the immunomodulatory potential of microbial-associated molecular patterns derived from the enteric bacterial microbiota

Patten

Collett

2013

Microbiology

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The human intestinal lumen represents one of the most densely populated microbial niches in the biological world and, as a result, the intestinal innate immune system exists in a constant state of stimulation. A key component in the innate defence system is the intestinal epithelial layer, which acts not only as a physical barrier, but also as an immune sensor. The expression of pattern recognition receptors, such as Toll-like receptors, in epithelial cells allows innate recognition of a wide range of highly conserved bacterial moieties, termed microbial-associated molecular patterns (MAMPs), from both pathogenic and non-pathogenic bacteria. To date, studies of epithelial immunity have largely concentrated on inflammatory pathogenic antigens; however, this review discusses the major types of MAMPs likely to be produced by the enteric bacterial microbiota and, using data from in vitro studies, animal model systems and clinical observations, speculates on their immunomodulatory potential. IntroductionThe intestine represents the body's largest mucosal surface, with the adult human intestine estimated to cover an area of about 250 m 2 (Artis, 2008). The highly folded luminal surface of the intestinal wall significantly increases absorption efficiency and, as such, is the largest surface area of the body exposed to the environment and its high microbial load (DeSesso & Jacobson, 2001). Humans have co-evolved with indigenous microbial populations, termed microbiota, which inhabit various niches of the body (Hooper et al., 2012) and the adult intestine is one of the most densely populated microbial habitations in the biological world (Artis, 2008). The enteric microbiota predominantly consists of bacteria, with estimated populations of~10 14 bacteria, with up to 500 species represented (Gill et al., 2006;Guarner & Malagelada, 2003); however, methanogenic archaea, eukaryotes (yeasts) and viruses (mainly bacteriophages) are also present (Lozupone et al., 2012). Due to the vast expanse of intestinal tissue exposed to the microbiota, the local innate immune system is in a constant state of stimulation, and a chronic, low-level proinflammatory response is characteristic of enteric immune homeostasis (Macpherson & Harris, 2004;Artis, 2008).The intestinal epithelium plays an active role in innate immunity, and pattern recognition receptors (PRRs) are utilized to detect the presence of bacteria and their associated antigens. PRRs are germline-encoded, sensory molecules which recognize a range of highly conserved bacterial motifs, termed 'pathogen-associated molecular patterns' (PAMPs) (Medzhitov, 2001). However, the ability of PRRs to recognize these bacterial moieties is not limited to just pathogens, and so the term 'microbial-associated molecular patterns' (MAMPs) may be more accurate (Medzhitov, 2001; Sanderson & Walker, 2007) and will be used throughout this review. Epithelium-associated, enteric immune cells, such as macrophages, dendritic cells, T-cells and B-cells, differentially express two major groups of PRRs, th...

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Nod1 acts as an intracellular receptor to stimulate chemokine production and neutrophil recruitment in vivo

Cited by 28 publications

References 41 publications

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

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

RICK/RIP2 Mediates Innate Immune Responses Induced through Nod1 and Nod2 but Not TLRs

Exploring the immunomodulatory potential of microbial-associated molecular patterns derived from the enteric bacterial microbiota

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