Journal article

TBK1 and IKK epsilon Act Redundantly to Mediate STING-Induced NF-kappa B Responses in Myeloid Cells

Katherine R Balka, Cynthia Louis, Tahnee L Saunders, Amber M Smith, Dale J Calleja, Damian B D'Silva, Fiona Moghaddas, Maximilien Tailler, Kate E Lawlor, Yifan Zhan, Christopher J Burns, Ian P Wicks, Jonathan J Miner, Benjamin T Kile, Seth L Masters, Dominic De Nardo

Cell Reports | CELL PRESS | Published : 2020

Abstract

Stimulator of Interferon Genes (STING) is a critical component of host innate immune defense but can contribute to chronic autoimmune or autoinflammatory disease. Once activated, the cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS)-STING pathway induces both type I interferon (IFN) expression and nuclear factor-κB (NF-κB)-mediated cytokine production. Currently, these two signaling arms are thought to be mediated by a single upstream kinase, TANK-binding kinase 1 (TBK1). Here, using genetic and pharmacological approaches, we show that TBK1 alone is dispensable for STING-induced NF-κB responses in human and mouse immune cells, as well as in vivo. We f..

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Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by NHMRC Clinical Practitioner Fellowship


Awarded by IRIISS


Funding Acknowledgements

We acknowledge G. Belz (Walter and Eliza Hall Institute, Parkville, Australia) for HSV-1 and D. Kalvakolanu (University of Maryland, MD, USA) for J2 recombinant retroviruses. We are very grateful to C.M. De Nardo (Monash University, Australia) for carefully proofreading the manuscript. This work was supported by Australian National Health and Medical Research Council (NHMRC) Project Grants (1099262 to S.L.M.; 1077750 to B.T.K.; 1145788 and 1162765 to K.E.L.) and a Program Grant (1113577 to B.T.K. and I.P.W.). Fellowships were from the NHMRC (to S.L.M. and B.T.K.), Victorian Endowment for Science Knowledge and Innovation (to S.L.M.), HHMI-Wellcome International Research Scholarship (to S.L.M.), the Sylvia and Charles Viertel Foundation (to S.L.M.), and a Monash University FMNHS Senior Postdoctoral Fellowship (to D.D.N.). I.P.W. is further supported by the Reid Charitable Trusts, a NHMRC Clinical Practitioner Fellowship (grant 1023407), Development Grant (1055374), IRIISS (grant 9000220), and a Victorian State Government Operational Infrastructure Support Grant.