Phospholipase Cγ2 (PLCγ2) Is Key Component in Dectin-2 Signaling Pathway, Mediating Anti-fungal Innate Immune Responses

C-type lectin receptors (CLRs) such as Dectin-2 function as pattern recognition receptors to sense fungal infection. However, the signaling pathways induced by these receptors remain largely unknown. Previous studies suggest that the CLR-induced signaling pathway may utilize similar signaling components as the B cell receptor-induced signaling pathway. Phospholipase C gamma 2 (PLC gamma 2) is a key component in B cell receptor signaling, but its role in other signaling pathways has not been fully characterized. Here, we show that PLC gamma 2 functions downstream of Dectin-2 in response to the stimulation by the hyphal form of Candida albicans, an opportunistic pathogenic fungus. Using PLC gamma 2-and PLC gamma 1-deficient macrophages, we found that the lack of PLC gamma 2, but not PLC gamma 1, impairs cytokine production in response to infection with C. albicans. PLC gamma 2 deficiency results in the defective activation of NF-kappa B and MAPK and a significantly reduced production of reactive oxygen species following fungal challenge. In addition, PLC gamma 2-deficient mice are defective in clearing C. albicans infection in vivo. Together, these findings demonstrate that PLC gamma 2 plays a critical role in CLR-induced signaling pathways, governing antifungal innate immune responses.