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<a href="http://doi.org/10.1371/journal.pone.0054804" target="_blank" rel="noreferrer noopener">http://doi.org/10.1371/journal.pone.0054804</a>
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Pages
11-11
Issue
1
Volume
8
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Title
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Extracellular ATP and Toll-Like Receptor 2 Agonists Trigger in Human Monocytes an Activation Program That Favors T Helper 17
Publisher
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PLOS ONE
Date
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2013
2013-01
Subject
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adaptive immunity; calcium ionophore; cd14(+) monocytes; cells; growth-factor-beta; host-defense; human dendritic cells; il-12 production; in-vivo; Science & Technology - Other Topics; serum-free conditions; th17
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Paustian C; Taylor P; Johnson T; Xu M; Ramirez N; Rosenthal K S; Shu S Y; Cohen P A; Czerniecki B J; Koski G K
Description
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Strategically-paired Toll-like receptor (TLR) ligands induce a unique dendritic cell (DC) phenotype that polarizes Th1 responses. We therefore investigated pairing single TLR ligands with a non TLR-mediated danger signal to cooperatively induce distinct DC properties from cultured human monocytes. Adenosine triphosphate (ATP) and the TLR2 ligand lipoteichoic acid (LTA) selectively and synergistically induced expression of IL-23 and IL-1 beta from cultured monocytes as determined by ELISA assays. Flow cytometric analysis revealed that a sizable sub-population of treated cells acquired DC-like properties including activated surface phenotype with trans-well assays showing enhanced migration towards CCR7 ligands. Such activated cells also preferentially deviated, in an IL-23 and IL-1-dependent manner, CD4(pos) T lymphocyte responses toward the IL-22(hi), IL-17(hi)/IFN-gamma(lo) Th17 phenotype in standard in vitro allogeneic sensitization assays. Although pharmacological activation of either ionotropic or cAMP-dependent pathways acted in synergy with LTA to enhance IL-23, only inhibition of the cAMP-dependent pathway antagonized ATP-enhanced cytokine production. ATP plus atypical lipopolysaccharide from P. gingivalis (signaling through TLR2) was slightly superior to E. coli-derived LPS (TLR4 ligand) for inducing the high IL-23-secreting DC-like phenotype, but greatly inferior for inducing IL-12 p70 production when paired with IFN-gamma, a distinction reflected in activated DCs' ability to deviate lymphocytes toward Th1. Collectively, our data suggest TLR2 ligands encountered by innate immune cells in an environment with physiologically-relevant levels of extracellular ATP can induce a distinct activation state favoring IL-23- and IL-1 beta-dependent Th17 type response.
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<a href="http://doi.org/10.1371/journal.pone.0054804" target="_blank" rel="noreferrer noopener">10.1371/journal.pone.0054804</a>
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Journal Article
2013
Adaptive Immunity
calcium ionophore
cd14(+) monocytes
Cells
Cohen P A
Czerniecki B J
growth-factor-beta
host-defense
human dendritic cells
il-12 production
in-vivo
Johnson T
Journal Article
Koski G K
Paustian C
PloS one
Ramirez N
Rosenthal K S
Science & Technology - Other Topics
serum-free conditions
Shu S Y
Taylor P
th17
Xu M