A TLR2 ligand suppresses inflammation by modulation of chemokine receptors and redirection of leukocyte migration.
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.
McKimmie
Clive S
CS
Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow Biomedical Research Centre, Glasgow, United Kingdam.
Moore
Mark
M
Fraser
Alasdair R
AR
Jamieson
Thomas
T
Xu
Damo
D
Burt
Claire
C
Pitman
Nick I
NI
Nibbs
Robert J
RJ
McInnes
Iain B
IB
Liew
Foo Y
FY
Graham
Gerard J
GJ
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007371:Interferon-gamma / Q000494:pharmacology; D007962:Leukocytes / Q000502:physiology*; D008024:Ligands; D008074:Lipoproteins / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000502:physiology*
D018925:Chemokines; D008024:Ligands; D008074:Lipoproteins; D016328:NF-kappa B; D012333:RNA, Messenger; D019707:Receptors, Chemokine; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate