Phospholipase Cγ2 (PLCγ2) is key component in Dectin-2 signaling pathway, mediating anti-fungal innate immune responses. J Biol Chem 2011 Dec 23;286(51):43651-43659
Date
11/02/2011Pubmed ID
22041900Pubmed Central ID
PMC3243564DOI
10.1074/jbc.M111.307389Scopus ID
2-s2.0-83755168978 (requires institutional sign-in at Scopus site) 50 CitationsAbstract
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.
Author List
Gorjestani S, Yu M, Tang B, Zhang D, Wang D, Lin XAuthor
Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntifungal Agents
Bone Marrow
Candida albicans
Immune System
Immunity, Innate
Lectins
Lectins, C-Type
MAP Kinase Signaling System
Macrophages
Male
Mice
Mice, Transgenic
NF-kappa B
Phospholipase C gamma
Reactive Oxygen Species
Signal Transduction