Sino-Norway Joint Lab On Fish Gastrointestinal Microbiota, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.
Immunology-Vaccinology, Department of Infectious and Parasitic Diseases, Faculty of Veterinary Medicine, University of Liège, B-4000, Liège, Belgium.
Microbiome. 2024 Nov 18;12(1):244. doi: 10.1186/s40168-024-01958-y.
Evidence has accumulated to demonstrate that intestinal microbiome can inhibit viral infection. However, our knowledge of the signaling pathways and identity of specific commensal microbes that mediate the antiviral response is limited. Zebrafish have emerged as a powerful animal model for study of vertebrate-microbiota interactions. Here, a rhabdoviral infection model in zebrafish allows us to investigate the modes of action of microbiome-mediated antiviral effect.
We observed that oral antibiotics-treated and germ-free zebrafish exhibited greater spring viremia of carp virus (SVCV) infection. Mechanistically, depletion of the intestinal microbiome alters TLR2-Myd88 signaling and blunts neutrophil response and type I interferon (IFN) antiviral innate immunity. Through 16S rRNA sequencing of the intestinal contents from control and antibiotic(s)-treated fish, we identified a single commensal bacterial species, Cetobacterium somerae, that can restore the TLR2- and neutrophil-dependent type I IFN response to restrict SVCV infection in gnotobiotic zebrafish. Furthermore, we found that C. somerae exopolysaccharides (CsEPS) was the effector molecule that engaged TLR2 to mediate the type I IFN-dependent antiviral function.
Together, our results suggest a conserved role of intestinal microbiome in regulating type I IFN antiviral response among vertebrates and reveal that the intestinal microbiome inhibits viral infection through a CsEPS-TLR2-type I IFN signaling axis in zebrafish. Video Abstract.
有证据表明肠道微生物组可以抑制病毒感染。然而，我们对于介导抗病毒反应的信号通路和特定共生微生物的了解还很有限。斑马鱼已成为研究脊椎动物-微生物群相互作用的有力动物模型。在这里，斑马鱼中的弹状病毒感染模型使我们能够研究微生物组介导的抗病毒作用的作用模式。
我们观察到口服抗生素处理和无菌斑马鱼表现出更高的鲤鱼病毒（SVCV）感染的春季血症。从机制上讲，肠道微生物组的耗竭会改变 TLR2-Myd88 信号传导，并减弱中性粒细胞反应和 I 型干扰素（IFN）抗病毒先天免疫。通过对来自对照和抗生素处理鱼的肠道内容物进行 16S rRNA 测序，我们鉴定出一种单一的共生细菌物种 Cetobacterium somerae，它可以恢复 TLR2 和中性粒细胞依赖性 I 型 IFN 反应，从而限制 gnotobiotic 斑马鱼中的 SVCV 感染。此外，我们发现 C. somerae 胞外多糖（CsEPS）是一种效应分子，它通过 TLR2 介导 I 型 IFN 依赖性抗病毒功能。
总的来说，我们的结果表明肠道微生物组在调节脊椎动物的 I 型 IFN 抗病毒反应中起着保守作用，并揭示了肠道微生物组通过 CsEPS-TLR2-I 型 IFN 信号轴抑制病毒感染在斑马鱼中。视频摘要。
