Journal article

Connexin-Dependent Transfer of cGAMP to Phagocytes Modulates Antiviral Responses

Genevieve Pepin, Dominic De Nardo, Christina L Rootes, Tomalika Ullah, Sumaiah S Al-Asmari, Katherine R Balka, Hong-Mei Li, Kylie M Quinn, Fiona Moghaddas, Stephane Chappaz, Benjamin T Kile, Eric F Morand, Seth L Masters, Cameron R Stewart, Bryan RG Williams, Michael Gantier

mBio | AMER SOC MICROBIOLOGY | Published : 2020

Abstract

Activation of cyclic GMP-AMP (cGAMP) synthase (cGAS) plays a critical role in antiviral responses to many DNA viruses. Sensing of cytosolic DNA by cGAS results in synthesis of the endogenous second messenger cGAMP that activates stimulator of interferon genes (STING) in infected cells. Critically, cGAMP can also propagate antiviral responses to uninfected cells through intercellular transfer, although the modalities of this transfer between epithelial and immune cells remain poorly defined. We demonstrate here that cGAMP-producing epithelial cells can transactivate STING in cocultured macrophages through direct cGAMP transfer. cGAMP transfer was reliant upon connexin expression by epithelial..

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Grants

Awarded by Australian National Health and Medical Research Council


Awarded by Australian Research Council


Awarded by Quebec Fonds de Recherche du Quebec (FRQS)-Sante


Funding Acknowledgements

This study was supported by the Australian National Health and Medical Research Council (1124485 and 1081167 to M.P.G. and research grant 1113577 and research fellowship 1063008 to B.T.K.); the Australian Research Council (140100594 Future Fellowship to M.P.G.); the Quebec Fonds de Recherche du Quebec (FRQS)-Sante (35071 to G.P.); and the Victorian Government's Operational Infrastructure Support Program.