title: Phospholipase Cγ2 (PLCγ2) is key component in Dectin-2 signaling pathway, mediating anti-fungal innate immune responses.
abstract: 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 Cγ2 (PLCγ2) 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 PLCγ2 functions downstream of Dectin-2 in response to the stimulation by the hyphal form of Candida albicans, an opportunistic pathogenic fungus. Using PLCγ2- and PLCγ1-deficient macrophages, we found that the lack of PLCγ2, but not PLCγ1, impairs cytokine production in response to infection with C. albicans. PLCγ2 deficiency results in the defective activation of NF-κB and MAPK and a significantly reduced production of reactive oxygen species following fungal challenge. In addition, PLCγ2-deficient mice are defective in clearing C. albicans infection in vivo. Together, these findings demonstrate that PLCγ2 plays a critical role in CLR-induced signaling pathways, governing antifungal innate immune responses.
authors: Departments of Molecular and Cellular Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030; Cancer Biology Program, The University of Texas, Graduate School of Biomedical Sciences, Houston, Texas 77030.
authors: Sara
authors: S
authors: Gorjestani
authors: Blood Research Institute, Blood Center of Wisconsin, Milwaukee, Wisconsin 53226; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
authors: Mei
authors: M
authors: Yu
authors: Departments of Molecular and Cellular Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030.
authors: Bing
authors: B
authors: Tang
authors: Institute of Bioscience and Technology, Texas A&M University, Houston, Texas 77030.
authors: Dekai
authors: D
authors: Zhang
authors: Blood Research Institute, Blood Center of Wisconsin, Milwaukee, Wisconsin 53226.
authors: Demin
authors: D
authors: Wang
authors: Departments of Molecular and Cellular Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030; Cancer Biology Program, The University of Texas, Graduate School of Biomedical Sciences, Houston, Texas 77030. Electronic address: xllin@mdanderson.org.
authors: Xin
authors: X
authors: Lin
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D001853:Bone Marrow / Q000378:metabolism; D002176:Candida albicans / Q000378:metabolism; D007107:Immune System; D007113:Immunity, Innate; D037102:Lectins / Q000737:chemistry; D037181:Lectins, C-Type / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D051966:Phospholipase C gamma / Q000276:immunology*; D017382:Reactive Oxygen Species; D015398:Signal Transduction
chemical_list: D000935:Antifungal Agents; D037102:Lectins; D037181:Lectins, C-Type; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C445340:dectin-2, mouse; D051966:Phospholipase C gamma