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Global transcriptional changes in response to cGAMP depend on STING in human THP-1 cells

Cellular & Molecular Immunology volume 15, pages 983–985 (2018)Cite this article

Cytosolic detection of foreign or misplaced self-DNA through the cGAS-STING pathway leads to cGAS-mediated synthesis of the second messenger molecule cGAMP. The immune signaling molecule STING binds cGAMP directly, and thus functions as a cGAMP sensor. Binding of cGAMP induces the activation of STING with the subsequent induction of anti-viral and proinflammatory genes. Currently, it is not known whether STING is the only cellular sensor of cGAMP, and it has not been reported whether stimulation with cGAMP can induce gene transcription independently of STING. Here we analyzed the global cGAMP-induced transcriptional gene program in STING-deficient human monocyte-derived THP-1 cells. We found that the global cGAMP-induced transcriptional response was dependent on STING and failed to identify groups of genes that were affected by cGAMP in the absence of STING. Our data therefore strongly indicate that STING is the sole receptor for cGAMP in human macrophages.

The innate immune system is the first line of defense against invading microorganisms and cancer cells. Incoming pathogens are sensed through a restricted number of receptors known as Pattern Recognition Receptors (PRRs), which recognize distinct evolutionarily conserved microbial structures termed Pathogen-Associated Molecular Patterns (PAMPs). Innate virus detection is highly dependent on intracellular sensors of viral nucleic acids, which include members of the Toll-like receptor family (TLRs), which detect DNA and RNA in endosomes, and receptors that recognize non-self RNA and DNA in the cytosol.1

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Acknowledgements

This research work was supported by Hørslevsfonden, Agnes and Poul Friis Fond, Brdr. Hartmanns fond, Oda og Hans Svenningsens Fond, Augustinus Fonden and Hede Nielsens Fond to C.K.H. In addition to C.C. Klestrup og Hustru Henriette Klestrup’s Mindefond, Direktør Jacob Madsen og Hustru Olga Madsen’s Fond, Den Bøhmske Fond, Lily Benthine Lunds Fond af 1.6.1978 and a PhD fellowship from the Department of Health Sciences at Aarhus University to ALH. DO’s salary was supported by a Carlsbergfonden International Research Fellowship.

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  1. These authors contributed equally: David Olagnier, Christian K. Holm.

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  1. Department of Biomedicine, Aarhus Research Center for Innate Immunology, Aarhus University, Aarhus, Denmark

    Anne Louise Hansen, Aske M. Brandtoft, Mette Nyegaard, Anne L. Thielke, David Olagnier & Christian K. Holm

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  1. Anne Louise Hansen
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Correspondence to Christian K. Holm.

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Hansen, A.L., Brandtoft, A.M., Nyegaard, M. et al. Global transcriptional changes in response to cGAMP depend on STING in human THP-1 cells. Cell Mol Immunol 15, 983–985 (2018). https://doi.org/10.1038/s41423-018-0035-x

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