Synergistic stimulation of human monocytes and dendritic cells by Toll-like receptor 4 and NOD1- and NOD2-activating agonists
- 4 August 2005
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 35 (8), 2459-2470
- https://doi.org/10.1002/eji.200526286
Abstract
Muropeptides are degradation products of bacterial peptidoglycan (PG) sensed by nucleotide‐binding oligomerization domain 1 (NOD1) and NOD2, members of a recently discovered family of pattern recognition molecules (PRM). One of these muropeptides, muramyl dipeptide (MDP) mediates cell signaling by NOD2, exerts adjuvant activity and synergizes with lipopolysaccharide (LPS) to induce pro‐inflammatory responses in vitro and in vivo. In contrast, few and contradictory results exist about the stimulatory capacity of NOD1 agonists. Thus, the ability of NOD1 (MurNAc‐L‐Ala‐γ‐D‐Glu‐meso‐diaminopimelic acid, MtriDAP) and NOD2 (MurNAc‐L‐Ala‐D‐isoGln, MDP; MurNAc‐L‐Ala‐γ‐D‐Glu‐L‐Lys, MtriLYS) agonists to activate primary human myeloid cells was examined. We show that both CD14+ monocytes and CD1a+ immature dendritic cells (DC) express NOD1 and NOD2 mRNA. Stimulation of primary human monocytes and DC with highly purified muropeptides (MtriDAP, MDP and MtriLYS) induces release of pro‐inflammatory cytokines. We reveal here that NOD1 as well as NOD2 agonists act cooperatively with LPS to stimulate the release of both pro‐ and anti‐inflammatory cytokines in these myeloid cell subsets. Finally, we report that NOD1 as well as NOD2 agonists synergize with sub‐active doses of LPS to induce DC maturation, demonstrating that NOD agonists act cooperatively with molecules sensed by Toll‐like receptor 4 to instruct the onset of adaptive immune responses.Keywords
This publication has 28 references indexed in Scilit:
- Septic shockThe Lancet, 2005
- Activation of CD38 by Interleukin-8 Signaling Regulates Intracellular Ca2+ Level and Motility of Lymphokine-activated Killer CellsPublished by Elsevier BV ,2005
- Toll-like receptor signallingNature Reviews Immunology, 2004
- An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acidNature Immunology, 2003
- 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions ConferenceCritical Care Medicine, 2003
- Nod2 Is a General Sensor of Peptidoglycan through Muramyl Dipeptide (MDP) DetectionJournal of Biological Chemistry, 2003
- Induction of Nod2 in Myelomonocytic and Intestinal Epithelial Cells via Nuclear Factor-κB ActivationJournal of Biological Chemistry, 2002
- The Origin of the Synergistic Effect of Muramyl Dipeptide with Endotoxin and PeptidoglycanPublished by Elsevier BV ,2002
- Nod2, a Nod1/Apaf-1 Family Member That Is Restricted to Monocytes and Activates NF-κBJournal of Biological Chemistry, 2001
- Differential Utilization of Cyclic ADP-Ribose Pathway by Chemokines to Induce the Mobilization of Intracellular Calcium in NK CellsBiochemical and Biophysical Research Communications, 1999