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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):43651-9

Date

11/02/2011

Pubmed ID

22041900

Pubmed Central ID

PMC3243564

DOI

10.1074/jbc.M111.307389

Scopus ID

2-s2.0-83755168978   36 Citations

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.

Author List

Gorjestani S, Yu M, Tang B, Zhang D, Wang D, Lin X

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antifungal 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
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5