Tissue specific innate immune responses impact viral infection in Drosophila.

IF 5.5 1区 医学 Q1 MICROBIOLOGY
Elisha Segrist, Steven Miller, Beth Gold, Yue Li, Sara Cherry
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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.

组织特异性先天免疫反应对果蝇病毒感染的影响
所有生物都能感知并应对病原体的挑战。要对抗感染不同细胞类型的病原体,就需要有组织特异性反应。环状二核苷酸(CDNs)是在病原体识别下游或由病原体本身产生的内源性物质,它与 STING 结合激活 NF-kB 依赖性抗微生物基因表达程序。果蝇组织对 CDNs 是否有不同的免疫反应仍是未知数。在这里,我们研究了组织特异性 CDN-STING 反应,并发现了在病毒感染中发挥重要作用的不同组织基因诱导模式的差异。通过组织和细胞特异性基因研究,我们发现脂肪体中的 dSTING 可控制 CDN 诱导的 dSTING 调节基因 1(Srg1)的表达,但不能控制 dSTING 调节基因 2(Srg2)或 3(Srg3)的表达。相反,胃肠道在很大程度上控制着 Srg2 和 Srg3 的表达。我们发现,Srg3 对天然蝇类病原体果蝇 C 病毒和人类节肢动物传播的裂谷热病毒(RVFV)有抗病毒作用,但对其他节肢动物传播的病毒(包括辛比病毒和登革热病毒)没有抗病毒作用。此外,我们还发现 Srg3 在控制 RVFV 感染卵巢方面起着重要作用,这对了解病毒和 RVFV 在蚊子中的垂直传播具有重要意义。总之,我们的研究强调了组织特异性反应在抗病毒免疫中的重要性,并突出了 CDN-STING 通路的复杂组织调控。
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来源期刊
PLoS Pathogens
PLoS Pathogens MICROBIOLOGY-PARASITOLOGY
自引率
3.00%
发文量
598
期刊介绍: Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.
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