Extracellular ATP and Toll-Like Receptor 2 Agonists Trigger in Human Monocytes an Activation Program That Favors T Helper 17

Christopher Paustian, Patricia Taylor, Terrence Johnson, Min Xu, Nancy Ramirez, Kenneth S. Rosenthal, Suyu Shu, Peter A Cohen, Brian J. Czerniecki, Gary K. Koski

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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-1β 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, CD4pos T lymphocyte responses toward the IL-22hi, IL-17hi/IFN-γlo 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-γ, 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-1β-dependent Th17 type response.

Original languageEnglish (US)
Article numbere54804
JournalPLoS One
Volume8
Issue number1
DOIs
StatePublished - Jan 31 2013

Fingerprint

Toll-Like Receptor 2
adenosine triphosphate
Interleukin-23
monocytes
agonists
Monocytes
Adenosine Triphosphate
Chemical activation
dendritic cells
Ligands
Dendritic Cells
Toll-Like Receptors
interleukin-1
Interleukin-1
Phenotype
phenotype
Assays
assays
T-cells
Lymphocytes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Paustian, C., Taylor, P., Johnson, T., Xu, M., Ramirez, N., Rosenthal, K. S., ... Koski, G. K. (2013). Extracellular ATP and Toll-Like Receptor 2 Agonists Trigger in Human Monocytes an Activation Program That Favors T Helper 17. PLoS One, 8(1), [e54804]. https://doi.org/10.1371/journal.pone.0054804

Extracellular ATP and Toll-Like Receptor 2 Agonists Trigger in Human Monocytes an Activation Program That Favors T Helper 17. / Paustian, Christopher; Taylor, Patricia; Johnson, Terrence; Xu, Min; Ramirez, Nancy; Rosenthal, Kenneth S.; Shu, Suyu; Cohen, Peter A; Czerniecki, Brian J.; Koski, Gary K.

In: PLoS One, Vol. 8, No. 1, e54804, 31.01.2013.

Research output: Contribution to journalArticle

Paustian, C, Taylor, P, Johnson, T, Xu, M, Ramirez, N, Rosenthal, KS, Shu, S, Cohen, PA, Czerniecki, BJ & Koski, GK 2013, 'Extracellular ATP and Toll-Like Receptor 2 Agonists Trigger in Human Monocytes an Activation Program That Favors T Helper 17', PLoS One, vol. 8, no. 1, e54804. https://doi.org/10.1371/journal.pone.0054804
Paustian, Christopher ; Taylor, Patricia ; Johnson, Terrence ; Xu, Min ; Ramirez, Nancy ; Rosenthal, Kenneth S. ; Shu, Suyu ; Cohen, Peter A ; Czerniecki, Brian J. ; Koski, Gary K. / Extracellular ATP and Toll-Like Receptor 2 Agonists Trigger in Human Monocytes an Activation Program That Favors T Helper 17. In: PLoS One. 2013 ; Vol. 8, No. 1.
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