Analysis of Drosophila STING Reveals an Evolutionarily Conserved Antimicrobial Function

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, associa...

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Bibliographic Details
Published in:Cell reports (Cambridge) 2018-06, Vol.23 (12), p.3537-3550.e6
Main Authors: Martin, Marina, Hiroyasu, Aoi, Guzman, R. Marena, Roberts, Steven A., Goodman, Alan G.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Anti-Infective Agents - metabolism
Antimicrobial Cationic Peptides - metabolism
antimicrobial peptide
CG7194
cGAS
Conserved Sequence
cricket paralysis virus
Drosophila melanogaster - metabolism
Drosophila melanogaster - microbiology
Drosophila Proteins - chemistry
Drosophila Proteins - metabolism
Evolution, Molecular
gene set enrichment analysis
IMD
invertebrate iridescent virus 6
Listeria monocytogenes
Listeria monocytogenes - physiology
Listeriosis - microbiology
Membrane Proteins - chemistry
Membrane Proteins - metabolism
NF-kappa B - metabolism
NFkB
Nucleotides - metabolism
Protein Binding
Relish
Signal Transduction
Transcription Factors - metabolism
Transcription, Genetic
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Summary: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. [Display omitted] •Drosophila STING (dmSTING) associates with cyclic dinucleotides•Flies knocked down or deleted for dmSTING are more susceptible to Listeria infection•DmSTING functions in mammalian cells and activates NF-κB signaling•DmSTING signals through the IMD pathway and stimulates Relish cleavage The vertebrate protein STING stimulates a potent interferon response to cyclic dinucleotides that are a byproduct of bacterial infections. Martin et al. demonstrate that a STING ortholog is evolutionarily conserved in Drosophila. DmSTING initiates an innate immune response to Listeria monocytogenes infection via activation of the NF-κB transcription factor Relish.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2018.05.029