title: Nod1 and Nod2 induce CCL5/RANTES through the NF-kappaB pathway.
abstract: 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-beta pathway, a major signaling cascade for the activation of CCL5 by viruses. In contrast, we identified a key role of the NF-kappaB pathway in Nod-dependent 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.
authors: Unité de Recherche Réponses Précoces aux Parasites et Immunopathologie, Institut Pasteur, Paris, France. cwerts@pasteur.fr
authors: Catherine
authors: C
authors: Werts
authors: Lionel
authors: L
authors: le Bourhis
authors: Jianguo
authors: J
authors: Liu
authors: Joao G
authors: JG
authors: Magalhaes
authors: Leticia A
authors: LA
authors: Carneiro
authors: Jörg H
authors: JH
authors: Fritz
authors: Silvia
authors: S
authors: Stockinger
authors: Viviane
authors: V
authors: Balloy
authors: Michel
authors: M
authors: Chignard
authors: Thomas
authors: T
authors: Decker
authors: Dana J
authors: DJ
authors: Philpott
authors: Xiaojing
authors: X
authors: Ma
authors: Stephen E
authors: SE
authors: Girardin
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D018946:Chemokine CCL5 / Q000378:metabolism*; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D003960:Diaminopimelic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D020672:I-kappa B Proteins / Q000378:metabolism; D007370:Interferon Type I / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D053474:Nod1 Signaling Adaptor Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction
chemical_list: C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D019742:Chemokines, CC; D020672:I-kappa B Proteins; D007370:Interferon Type I; D016328:NF-kappa B; D053474:Nod1 Signaling Adaptor Protein; D053473:Nod2 Signaling Adaptor Protein; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D003960:Diaminopimelic Acid; C034330:FK 156