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Synergistic enhancement of Toll-like receptor responses by NOD1 activation

journal contribution
posted on 2023-05-17, 08:08 authored by van Heel, DA, Ghosh, S, Butler, M, Hunt, K, Foxwell, BMJ, Mengin-Lecreulx, D, Playford, RJ
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.

History

Publication title

European Journal of Immunology

Volume

35

Issue

8

Pagination

2471-2476

ISSN

0014-2980

Department/School

College Office - College of Health and Medicine

Publisher

Wiley-V C H Verlag Gmbh

Place of publication

Po Box 10 11 61, Weinheim, Germany, D-69451

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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