Nod1 Detects a Unique Muropeptide from Gram-Negative Bacterial Peptidoglycan

Girardin, Stephen E.; Boneca, Ivo Gomperts; Carneiro, Letícia A.M.; Antignac, Aude; Jéhanno, Muguette; Viala, Jérôme; Tedin, Karsten; Taha, Muhamed‐Kheir; Labigne, Agnès; Zähringer, Ulrich; Coyle, Anthony J.; DiStefano, Peter S.; Bertin, John; Sansonetti, Philippe J.; Philpott, Dana J.

doi:10.1126/science.1084677

Cited by 1,402 publications

(1,145 citation statements)

References 28 publications

Supporting

Mentioning

1,112

Contrasting

Unclassified

Order By: Relevance

“…It is possible that distinct TLR are triggered on DC by live and heat-killed bacteria. Alternatively, intracellular pattern recognition receptors such as nucleotide-binding oligomerization domain proteins (NOD) [26] might be required to fully activate DC. This trigger might be selectively activated by live, cytosol-invasive bacteria [27].…”

Section: Discussionmentioning

confidence: 99%

Distinct in vivo dendritic cell activation by live versus killed Listeria monocytogenes

et al. 2005

View full text Add to dashboard Cite

Immunization of mice with live or heat-killed Listeria monocytogenes (HKLM) efficiently primes pathogen-specific CD8 + T cells. T lymphocytes primed by HKLM, however, undergo attenuated proliferation and do not fully differentiate. Thus, only infection with live bacteria induces long-term, CD8 + T cell-mediated protective immunity. In this study we demonstrate that live and heat-killed bacteria, while both associating with Mac-3 + CD11b hi cells, localize to distinct splenic areas following intravenous inoculation. While HKLM localize to the marginal zone and the splenic red pulp, live L. monocytogenes are carried to the T cell zone of splenic white pulp. Despite these differences, in vivo depletion of CD11c-expressing cells prevents priming of naive T cells by either HKLM or live L. monocytogenes. Analysis of CD11c hi dendritic cells (DC) reveals that infection with live L. monocytogenes induces higher levels of CD40, CD80 and CD86 expression than immunization with HKLM. Our results suggest that CD8 + T cell priming following HKLM immunization or live infection is mediated by DC and that the disparate outcomes of priming can be attributed to suboptimal conditioning of DC in the absence of live, cytosol-invasive bacteria.

show abstract

Section: Discussionmentioning

confidence: 99%

Distinct in vivo dendritic cell activation by live versus killed Listeria monocytogenes

et al. 2005

View full text Add to dashboard Cite

show abstract

“…51 Nod1, in contrast, has a narrow specificity and recognizes only DAP-type PG, which constitutes a signature of most Gram-negative bacterial PGs. 43 Nod1 detects efficiently the naturally occurring muropeptide GM-L-Ala-DGlu-mesoDAP, but the minimal motif found to activate human Nod1 is the dipeptide D-Glu-mesoDAP. 45,50 Interestingly, species specificity of Nod1 recognition has been shown for the tracheal cytotoxin (TCT).…”

Section: Nods and Pg Motifsmentioning

confidence: 99%

“…Originally thought to be a TLR2 agonist, PG activates cells through Nod proteins. [42][43][44][45] TLR2 stimulatory activity of PG can be attributed to contaminating lipoproteins and/or lipoteichoic acid. 46 This question remains controversial since Dziarski and colleagues published that TLR2 senses soluble PG from Staphylococcus aureus.…”

Section: Nods and Pg Motifsmentioning

confidence: 99%

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

2006

View full text Add to dashboard Cite

Innate immunity to microorganisms in mammals has gained a substantial interest during the last decade. The discovery of the Toll-like receptor (TLR) family has allowed the identification of a class of membrane-spanning receptors dedicated to microbial sensing. TLRs transduce downstream signaling via their intracellular Toll-interleukin-1 receptor (TIR) domain. More recently, the role of intracellular microbial sensors has been uncovered. These molecules include the Nod-like receptors Nod1, Nod2, Ipaf and Nalps, together with the helicase domain-containing antiviral proteins RIG-I and Mda-5. The intracellular microbial sensors lack the TIR domain, but instead transduce downstream signals via two domains also implicated in homophilic protein-protein interactions, the caspase activation and recruitment domain (CARD) and PYRIN domains. In light with these recent findings, we propose that TIR, CARD and PYRIN domains represent the three arms of innate immune detection of microorganisms in mammals.

show abstract

“…Nod1 and Nod2 both detect peptidoglycan substructures from bacterial peptidoglycan, a cell wall component of virtually all bacteria [9][10][11][12][13][14]. While Nod2 detects muramyl dipeptide (MurNAc-L-Ala-D-Glu, MDP) [11,13], the human form of Nod1 senses a diaminopimelic acid (DAP)-containing muramyl tripeptide (muramyl-L-Ala-D-Glu-mesoDAP, M-TriDAP) [9,10], and murine Nod1 preferentially detects a DAP-containing muramyl tetrapeptide (muramyl-L-Ala-D-Glu-meso-DAP-D-Ala) [14].…”

Section: Introductionmentioning

confidence: 99%

“…While Nod2 detects muramyl dipeptide (MurNAc-L-Ala-D-Glu, MDP) [11,13], the human form of Nod1 senses a diaminopimelic acid (DAP)-containing muramyl tripeptide (muramyl-L-Ala-D-Glu-mesoDAP, M-TriDAP) [9,10], and murine Nod1 preferentially detects a DAP-containing muramyl tetrapeptide (muramyl-L-Ala-D-Glu-meso-DAP-D-Ala) [14]. 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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2007

View full text Add to dashboard Cite

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.

show abstract

Nod1 Detects a Unique Muropeptide from Gram-Negative Bacterial Peptidoglycan

Cited by 1,402 publications

References 28 publications

Distinct in vivo dendritic cell activation by live versus killed Listeria monocytogenes

Distinct in vivo dendritic cell activation by live versus killed Listeria monocytogenes

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

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

Contact Info

Product

Resources

About