A TLR2 ligand suppresses inflammation by modulation of chemokine receptors and redirection of leukocyte migration

McKimmie, C. S. et al. (2009) A TLR2 ligand suppresses inflammation by modulation of chemokine receptors and redirection of leukocyte migration. Blood, 113(18), pp. 4224-4231. (doi:10.1182/blood-2008-08-174698) (PMID:19202130)

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Abstract

Toll-like receptors orchestrate rapid local protective innate-immune responses to invading pathogens and optimize leukocyte priming of subsequent adaptive responses. Paradoxically, systemic excess of the TLR2 ligand, bacterial lipoprotein (BLP), suppresses peripheral inflammatory responses. Here, we demonstrate that this phenomenon is regulated via the TLR2-dependent, cell-autonomous down-regulation of inflammatory chemokine receptor expression on a variety of leukocyte subsets. Remarkably, BLP mediated no effect on constitutive chemokine receptor expression. By tracking adoptively transferred wild-type and TLR2(-/-) leukocytes in vivo, we observed that BLP mediated chemokine receptor switching directed leukocytes away from inflamed sites toward secondary lymphoid organs. These data highlight a novel role for TLR ligands, such as BLP, in regulating leukocyte retention and migration away from innate immune lesions via discrete constitutive and inflammatory chemokine receptor regulation

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Professor Foo and McInnes, Professor Iain and Xu, Dr Damo and Fraser, Dr Alasdair and Moore, Mrs Margaret and Nibbs, Professor Robert and McKimmie, Dr Clive and Graham, Professor Gerard and Burt, Miss Claire
Authors: McKimmie, C. S., Moore, M., Fraser, A. R., Xu, D., Jamieson, T., Burt, C., Pitman, N. I., Nibbs, R. J., McInnes, I. B., Liew, F. Y., and Graham, G. J.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Blood
Publisher:American Society of Hematology
ISSN:0006-4971
ISSN (Online):1528-0020
Published Online:06 February 2009

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
453811Toll like receptors and chemokine receptors - 2 interconnected arms of the innate immune responseGerard GrahamMedical Research Council (MRC)G0700120Infection Immunity and Inflammation Medicine
486461The role of IL-35 in infection and inflammationFoo LiewMedical Research Council (MRC)G0801198Infection Immunity and Inflammation Medicine