Biology subjects

Jiao, R.

Publications and source records attributed to Jiao, R..

2 recordsLinked to original sources

bioRxiv2023

A novel virus-induced cyclic dinucleotide, 2'3'-c-di-GMP, mediates STING-dependent antiviral immunity in Drosophila

In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2'3'-cGAMP. This CDN binds to and activates the protein STING to trigger immunity. We recently discovered in the model organism Drosophila melanogaster two cGAS-like receptors (cGLRs) that activate STING-dependent antiviral immunity and can produce 3'2'-cGAMP, in addition to 2'3'-cGAMP. Here we explore CDN-mediated immunity in 14 different Drosophila species covering 50 million years of evolution and report that 2'3'-cGAMP and 3'2'-cGAMP fail to control infection by Drosophila C virus in D. serrata, D. sechellia and D. mojavensis. Using an accurate and sensitive mass spectrometry method, we discover an unexpected diversity of CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster, including a novel CDN, 2'3'-c-di-GMP. We show that 2'3'-c-di-GMP is the most potent STING agonist identified so far in D. melanogaster and that this molecule also activates a strong antiviral transcriptional response in D. serrata. Our results shed light on the evolution of cGLRs in flies and provide a basis for the understanding of the function and regulation of this emerging family of PRRs in animal innate immunity.

immunology↗

bioRxiv2020

The BaramicinA gene is required at several steps of the host defense against Enterococcus faecalis and Metarhizium robertsii in a septic wound infection model in Drosophila melanogaster

The Drosophila systemic immune response against many Gram-positive bacteria and fungi is mediated by the Toll pathway. How Toll-regulated effectors actually fulfill this role remains poorly understood as the known antimicrobial peptide (AMP) genes it controls are essentially active only against filamentous fungi and not against Gram-positive bacteria or yeasts. BaramicinA gene expression is transcriptionally regulated by the Toll pathway. BaraA encodes a polyprotein precursor that releases processed proteins into the hemolymph upon immune challenge. Here, we demonstrate that BaraA is required specifically in the host defense against Enterococcus faecalis and against the entomopathogenic fungus Metarhizium robertsii. It does so by protecting the fly from the action of distinct toxins secreted by Gram-positive and fungal pathogens but not by directly attacking them. Thus, in complement to the current paradigm, innate immunity can cope with toxins, effectively, through the secretion of peptides that are not AMPs, independently of xenobiotics detoxification pathways.

immunology↗