cGAS-like receptors drive a systemic STING-dependent host response in Drosophila
cGAS-like receptor (cGLR)-stimulator of interferon genes (STING) recently emerged as an important pathway controlling viral infections in invertebrates. However, its exact contribution at the organismal level remains uncharacterized. Here, we use STING::GFP knockin reporter Drosophila flies to document activation of the pathway in vivo. Four tissues strongly respond to injection of the cyclic dinucleotide 3'2'- cyclic guanosine monophosphate-adenosine monophosphate (cGAMP): the central nervous system, midgut, Malpighian tubules, and genital ducts. The pattern of STING::GFP induction in flies injected with 3'2'-cGAMP or infected by two viruses with different tropism suggests that the reporter is induced by a systemic signal produced in virus-infected cells. Accordingly, ectopic expression of cGLR2 in the fat body induces STING signaling in remote tissues and a cGLR1/2-dependent activity is transferred to females during mating. Furthermore, viral infection can alter sleep in a cGLR1/2- and STING-dependent manner. Altogether, our results reveal a contribution of cyclic dinucleotide signaling to a systemic host response to viral infection in Drosophila.
Authors
- Carine Meignin (ORCID: https://orcid.org/0000-0002-6588-9045)
- Huimin Deng (ORCID: https://orcid.org/0000-0001-8834-8172)
- Jean‐Luc Imler (ORCID: https://orcid.org/0000-0003-0740-8319)
- Xianlong Ai
- Haoming Li
- Jingxian Huang
- Xiaoqing Lin (ORCID: https://orcid.org/0000-0002-1751-5348)
- Hua Cai (ORCID: https://orcid.org/0000-0002-6697-652X)
- Di Chen (ORCID: https://orcid.org/0000-0002-2186-7717)
- Xiaohan Zhang (ORCID: https://orcid.org/0000-0003-1531-3061)
- Xiaoyan Li (ORCID: https://orcid.org/0009-0007-8953-3610)
- Ting Yin (ORCID: https://orcid.org/0000-0003-4142-5112)
- Long Tan (ORCID: https://orcid.org/0000-0002-0496-6043)
- Xiuqing Zhang (ORCID: https://orcid.org/0000-0003-4578-8359)
- Yuqiang Chen (ORCID: https://orcid.org/0000-0003-2058-3752)
- Ziming Wei
- Junhui Zhang
Institutions
- Centre National de la Recherche Scientifique (FR)
- Chinese Academy of Sciences (CN)
- Guangzhou Institutes of Biomedicine and Health (CN)
- State Key Laboratory of Respiratory Disease (CN)
- Institut de Biologie Moléculaire et Cellulaire (FR)
- Université de Strasbourg (FR)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.115081
- Citations
- 18
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 9.77
Funders
- Agence Nationale de la Recherche
- China Postdoctoral Science Foundation
- Centre National de la Recherche Scientifique