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

19 Scopus citations

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

ASJC Scopus subject areas

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

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    Paustian, C., Taylor, P., Johnson, T., Xu, M., Ramirez, N., Rosenthal, K. S., Shu, S., Cohen, P. A., Czerniecki, B. J., & 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