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Analysis of Drosophila STING Reveals an Evolutionarily Conserved Antimicrobial Function
Marina Martin1, Aoi Hiroyasu1, R Marena Guzman1
1School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
Cell Reports
|June 21, 2018
Summary
The STING protein in Drosophila initiates an innate immune response against bacterial infection by activating the NF-κB pathway. This conserved immune mechanism enhances host defense in flies, similar to vertebrates.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- STING is a key intracellular sensor in vertebrate innate immunity, crucial for detecting cyclic dinucleotides and initiating type I interferon responses.
- Pathogenic infections trigger innate immune responses essential for host survival.
Purpose of the Study:
- To investigate the presence and function of a STING ortholog in Drosophila.
- To determine the role of Drosophila STING (dmSTING) in innate immunity and host defense against bacterial infection.
Main Methods:
- Identified and characterized a STING ortholog (dmSTING) in Drosophila.
- Infected Drosophila with Listeria monocytogenes to assess dmSTING's role in immune response.
- Analyzed the activation of the NF-κB transcription factor Relish and the IMD pathway.
- Evaluated the impact of dmSTING on host survival and bacterial load.
Main Results:
- Drosophila possesses a functional STING ortholog (dmSTING) that binds cyclic dinucleotides.
- dmSTING activates the NF-κB transcription factor Relish and the IMD pathway following Listeria monocytogenes infection.
- Activation of dmSTING significantly reduces Listeria-induced lethality and bacterial load in Drosophila.
- dmSTING triggers an innate immune response independently of a known cyclic guanosine monophosphate (GMP)-AMP synthase (cGAS) ortholog.
Conclusions:
- STING is an evolutionarily conserved antimicrobial effector in both flies and mammals.
- dmSTING plays a critical role in Drosophila's host defense against pathogenic infections.
- The findings highlight a conserved innate immune pathway involving STING across different species.
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