Analysis of Drosophila STING Reveals an Evolutionarily Conserved Antimicrobial Function
Open accessAbstract
The vertebrate protein STING, an intracellular sensor of cyclic dinucleotides, is critical to the innate immune response and the induction of type I interferon during pathogenic infection. Here, we show that a STING ortholog (dmSTING) exists in Drosophila, which, similar to vertebrate STING, associates with cyclic dinucleotides to initiate an innate immune response. Following infection with Listeria monocytogenes, dmSTING activates an innate immune response via activation of the NF-κB transcription factor Relish, part of the immune deficiency (IMD) pathway. DmSTING-mediated activation of the immune response reduces the levels of Listeria-induced lethality and bacterial load in the host. Of significance, dmSTING triggers an innate immune response in the absence of a known functional cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) ortholog in the fly. Together, our results demonstrate that STING is an evolutionarily conserved antimicrobial effector between flies and mammals, and it comprises a key component of host defense against pathogenic infection in Drosophila.
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In Drosophila, DNA sensing and the cGAS-STING axis are absent, while RNA sensing through Dicer-2 and a TLR and the NF-kB pathway are present.
“More primitive mechanisms based on RNA sensing though Dicer-2 and a TLR are present, as is the NF-kB pathway, which activates the production of antimicrobial peptides; however, DNA sensing and the cGAS-STING axis are absent103.”
From The role of retrotransposable elements in ageing and age-associated diseases (2021) · cites this paper as [103]
The Introduction and Discussion describe Dicer-2 sensing viral RNA, Toll and IMD signaling through NF-κB to induce antimicrobial peptides, and no functional cGAS–STING axis in Drosophila. They do not describe Toll as an RNA sensor or establish that all DNA sensing is absent. The paper also identifies a functional Drosophila STING protein that senses cyclic dinucleotides. (LLM, conf=0.86)
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References 81 · Cited by 173
- Authors
- Martin, M., Hiroyasu, A., Guzman, R. M., Roberts, S. A., & Goodman, A. G.
- Affiliations
- Washington State University (US)
- Corresponding author
- Goodman, Alan G.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 23
- Issue
- 12
- Pages
- 3537-3550.e6
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC6114933
- OpenAlex
- W2809254765
- Cited by
- 173
- References
- 81
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 28 · 2023: 17 · 2022: 25 · 2021: 25 · 2020: 22 · 2019: 20 · 2018: 6
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Washington State University
- Marvel Shields Autzen and R. Keith Farrell Endowed Memorial Funds
- NIH Public Health Service (R00AI106963, R21AI128103)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Invertebrate Immune Response Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- STING, Drosophila, innate immunity, cyclic dinucleotides, Listeria monocytogenes, Relish, NF-κB signaling, immune deficiency pathway, antimicrobial defense, innate immunity evolution, type I interferon
- MeSH terms
- STING Protein, Amino Acid Sequence, Animals, Anti-Infective Agents, Drosophila melanogaster, Listeriosis, Listeria monocytogenes, Membrane Proteins, Nucleotides, Protein Binding, Transcription Factors, Transcription, Genetic, Signal Transduction, NF-kappa B, Conserved Sequence, Evolution, Molecular, Antimicrobial Cationic Peptides, Drosophila Proteins
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