Nod1 and Nod2 induce CCL5/RANTES through the NF-kappaB pathway
Catherine Werts1, Lionel le Bourhis, Jianguo Liu
1Unité de Recherche Réponses Précoces aux Parasites et Immunopathologie, Institut Pasteur, Paris, France. cwerts@pasteur.fr
European Journal of Immunology
|August 21, 2007
Summary
Nod1 and Nod2 proteins activate the release of CCL5/RANTES chemokine. This discovery reveals a new role for Nod proteins in bacterial infections, independent of interferon-beta signaling.
Area of Science:
- Immunology
- Molecular Biology
Background:
- Nod-like receptor (NLR) proteins Nod1 and Nod2 detect bacterial peptidoglycan, crucial for innate immunity.
- Nod1 is known to induce neutrophil-attracting chemokines like CXCL8/IL-8 and CXCL1/CXCL2.
Purpose of the Study:
- To investigate if Nod proteins stimulate the release of CCL5/RANTES, a chemokine that attracts various immune cells but not neutrophils.
- To elucidate the signaling pathways involved in Nod-dependent CCL5/RANTES secretion.
Main Methods:
- Murine macrophages were stimulated with Nod1 and Nod2 agonists.
- CCL5/RANTES secretion was measured in vitro.
- Nod1 and Nod2 agonists were administered intraperitoneally to mice, and CCL5/RANTES levels in blood were assessed.
- The role of interferon-beta and NF-kappaB pathways in Nod-dependent CCL5/RANTES production was examined.
Main Results:
- Activation of both Nod1 and Nod2 led to significant CCL5/RANTES secretion by murine macrophages.
- In vivo, Nod1 or Nod2 agonist injection rapidly increased blood CCL5/RANTES levels.
- Nod-dependent CCL5/RANTES secretion was not linked to interferon-beta pathway activation.
- The NF-kappaB pathway was identified as critical for Nod-dependent stimulation of the CCL5/RANTES promoter.
Conclusions:
- Nod1 and Nod2 proteins induce the secretion of CCL5/RANTES.
- This represents a novel downstream target for Nod proteins in bacterial infections.
- The NF-kappaB pathway, not interferon-beta, mediates Nod-dependent CCL5/RANTES release, highlighting a specific immune response mechanism.
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