Requirement of phospholipase C-γ2 (PLCγ2) for dectin-1-induced antigen presentation and induction of TH1/TH17 polarization

Ilaria Tassi, Marina Cella, Iris Castro, Susan Gilfillan, Wasif N. Khan, Marco Colonna

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

DC recognize microbial components through an array of receptors known as PRR. PRR initiate intracellular signals, which engender DC with the capacity to stimulate T-cell responses. Dectin-1 is a PRR that recognizes β-glucan, a major constituent of many fungi's outer cell wall. Here we show that Dectin-1 activates DC through phospholipase (PLC)γ2 signaling. PLCγ2-deficient DC were unable to expand antigen-specific T cells and induce TH1 and TH17 differentiation in response to β-glucan. Mechanistically, PLCγ2-deficiency impaired the capacity of DC to secrete polarizing cytokines following exposure to β-glucan. Dectin-1 required PLCγ2 to activate MAPK, AP-1 and NF-κB, which induce cytokine gene expression. Moreover, PLCγ2 controlled Dectin-1-mediated NFAT activation and induction of NFAT-dependent genes such as IL-2, cyclooxigenase-2 and Egr transcription factors.We conclude that PLCγ2 is a crucial signaling mediator that modifies DC gene expression program to activate DC responses to β-glucan-containing pathogens.

Original languageEnglish
Pages (from-to)1369-1378
Number of pages10
JournalEuropean Journal of Immunology
Volume39
Issue number5
DOIs
StatePublished - May 1 2009

Keywords

  • DC
  • Dectin-1
  • PLCγ
  • Signaling

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