Publications
2023
H Cai, L Li, KM Slavik, J Huang, T Yin, X Ai, L Hédelin, G Haas, Z Xiang, Y Yang, X Li, Y Chen, Z Wei, H Deng, D Chen, R Jiao, N Martins, C Meignin, PJ Kranzusch, JL Imler
The virus-induced cyclic dinucleotide 2'3'-c-di-GMP mediates STING-dependent antiviral immunity in Drosophila Journal Article
In: Immunity, vol. 56, iss. 9, pp. 1991-2005, 2023.
Abstract | Links | BibTeX | Tags: c-di-GMP, cGAMP, cGAS, cGLR, cyclic dinucleotide, Drosophila, Evolution, Hua, imler, M3i, meignin, pattern recognition receptor, STING, virus
@article{nokey,
title = {The virus-induced cyclic dinucleotide 2'3'-c-di-GMP mediates STING-dependent antiviral immunity in Drosophila},
author = {Cai H and Li L and Slavik KM and Huang J and Yin T and Ai X and Hédelin L and Haas G and Xiang Z and Yang Y and Li X and Chen Y and Wei Z and Deng H and Chen D and Jiao R and Martins N and Meignin C and Kranzusch PJ and Imler JL},
editor = {Elsevier Inc. },
url = {https://pubmed.ncbi.nlm.nih.gov/37659413/},
doi = {10.1016/j.immuni.2023.08.006 },
year = {2023},
date = {2023-09-12},
urldate = {2023-09-12},
journal = {Immunity},
volume = {56},
issue = {9},
pages = {1991-2005},
abstract = {In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2'3'-cGAMP, which triggers STING-dependent immunity. In Drosophila melanogaster, two cGAS-like receptors (cGLRs) produce 3'2'-cGAMP and 2'3'-cGAMP to activate STING. We explored CDN-mediated immunity in 14 Drosophila species covering 50 million years of evolution and found that 2'3'-cGAMP and 3'2'-cGAMP failed to control infection by Drosophila C virus in D. serrata and two other species. We discovered diverse CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster, including 2'3'-c-di-GMP. This CDN was a more potent STING agonist than cGAMP in D. melanogaster and it also activated a strong antiviral transcriptional response in D. serrata. Our results shed light on the evolution of cGLRs in flies and provide a basis for understanding the function and regulation of this emerging family of pattern recognition receptors in animal innate immunity. },
keywords = {c-di-GMP, cGAMP, cGAS, cGLR, cyclic dinucleotide, Drosophila, Evolution, Hua, imler, M3i, meignin, pattern recognition receptor, STING, virus},
pubstate = {published},
tppubtype = {article}
}
In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2'3'-cGAMP, which triggers STING-dependent immunity. In Drosophila melanogaster, two cGAS-like receptors (cGLRs) produce 3'2'-cGAMP and 2'3'-cGAMP to activate STING. We explored CDN-mediated immunity in 14 Drosophila species covering 50 million years of evolution and found that 2'3'-cGAMP and 3'2'-cGAMP failed to control infection by Drosophila C virus in D. serrata and two other species. We discovered diverse CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster, including 2'3'-c-di-GMP. This CDN was a more potent STING agonist than cGAMP in D. melanogaster and it also activated a strong antiviral transcriptional response in D. serrata. Our results shed light on the evolution of cGLRs in flies and provide a basis for understanding the function and regulation of this emerging family of pattern recognition receptors in animal innate immunity.