1. Tissue specific innate immune responses impact viral infection in Drosophila.
- Author
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Segrist, Elisha, Miller, Steven, Gold, Beth, Li, Yue, and Cherry, Sara
- Abstract
All organisms sense and respond to pathogenic challenge. Tissue-specific responses are required to combat pathogens infecting distinct cell types. Cyclic dinucleotides (CDNs) are produced endogenously downstream of pathogen recognition or by pathogens themselves which bind to STING to activate NF-kB-dependent antimicrobial gene expression programs. It remains unknown whether there are distinct immune responses to CDNs in Drosophila tissues. Here, we investigated tissue specific CDN-STING responses and uncovered differences in gene-induction patterns across tissues that play important roles in viral infections. Using tissue-and cell-specific genetic studies we found that dSTING in the fat body controls CDN-induced expression of dSTING-regulated gene 1 (Srg1) but not dSTING-regulated gene 2 (Srg2) or 3 (Srg3). In contrast, the gastrointestinal tract largely controls expression of Srg2 and Srg3. We found that Srg3 is antiviral against the natural fly pathogen Drosophila C virus and the human arthropod-borne Rift Valley Fever virus (RVFV), but not other arthropod-borne viruses including Sindbis virus and dengue virus. Furthermore, we found that Srg3 has an important role in controlling RVFV infection of the ovary which has important implications in understanding vertical transmission of viruses and RVFV in mosquitoes. Overall, our study underscores the importance of tissue-specific responses in antiviral immunity and highlights the complex tissue regulation of the CDN-STING pathway. Author summary: The cyclic dinucleotide (CDN)-STING pathway (CDN-STING pathway) is a highly conserved innate immune pathway that stimulates the production of antiviral genes in response to infection. We found that diverse fly tissues respond to CDN stimulation, but dSTING regulates distinct subsets of genes across tissues. We also found that the CDN regulated gene, dSTING regulated gene 3 (Srg3), was antiviral against the human arbovirus Rift Valley Fever virus but not dengue or Sindbis virus. Furthermore, we found that Srg3 has an important role in controlling RVFV infection of the ovary which has important implications in vertical transmission of viruses such as RVFV. These findings highlight the tissue-specific activity of the CDN-STING pathway and emphasize the importance of understanding how different tissues sense and integrate immune signals during pathogenic challenge. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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