Requirement of phospholipase C-γ2 (PLCγ2) for dectin-1-induced antigen presentation and induction of T_H1/T_H17 polarization

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 T_H1 and T_H17 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.