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

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.

journal_name

Blood

journal_title

Blood

authors

McKimmie CS,Moore M,Fraser AR,Jamieson T,Xu D,Burt C,Pitman NI,Nibbs RJ,McInnes IB,Liew FY,Graham GJ

doi

10.1182/blood-2008-08-174698

subject

Has Abstract

pub_date

2009-04-30 00:00:00

pages

4224-31

issue

18

eissn

0006-4971

issn

1528-0020

pii

blood-2008-08-174698

journal_volume

113

pub_type

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