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Synergistic enhancement of Toll-like receptor responses by NOD1 activation


van Heel, DA and Ghosh, S and Butler, M and Hunt, K and Foxwell, BMJ and Mengin-Lecreulx, D and Playford, RJ, Synergistic enhancement of Toll-like receptor responses by NOD1 activation, European Journal of Immunology, 35, (8) pp. 2471-2476. ISSN 0014-2980 (2005) [Refereed Article]

DOI: doi:10.1002/eji.200526296


NOD1 is an intracellular pattern-recognition receptor specific for Gram-negative peptidoglycan that is important in host response to infections (e.g. Helicobacter pylori and Shigella flexneri). Genetic variation in NOD1 predisposes to asthma and inflammatory bowel disease. Functional responses have not previously been studied in primary human cells. NOD1 activation by low nanomolar concentrations of the specific muropeptide ligand M-TriDAP induced minimal human peripheral blood mononuclear cell TNF-α, IL-1β or IL-10 secretion, but synergistically increased Toll-like receptor (TLR)-induced responses. Synergistic responses were seen across multiple ligands (to TLR1/2, 2/6, 4, 5, 7/8) and a broad range of cytokine secretion (TNF-α, IL-1α, IL-1β, IL-4, IL-6, IL-10, GM-CSF). Synergy was also observed in the allogeneic mixed lymphocyte reaction. These responses were similar in cells homozygous for Crohn's disease-associated NOD2 mutations. In contrast to cell lines, primary human peripheral blood mononuclear cells respond to NOD1 muropeptides at ∼ 100-fold lower concentrations. Cross-talk between cytosolic NOD1 and membrane-bound TLR enhances responses to the multiple antigens simultaneously presented by a microbe. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Gastroenterology and hepatology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Playford, RJ (Professor Ray Playford)
ID Code:72946
Year Published:2005
Web of Science® Times Cited:119
Deposited By:Research Division
Deposited On:2011-09-05
Last Modified:2011-09-05

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