The intestinal microbiome and Cetobacterium somerae inhibit viral infection through TLR2-type I IFN signaling axis in zebrafish

Abstract Background 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...

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Main Authors: Hui Liang, Ming Li, Jie Chen, Wenhao Zhou, Dongmei Xia, Qianwen Ding, Yalin Yang, Zhen Zhang, Chao Ran, Zhigang Zhou
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Microbiome
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Online Access:https://doi.org/10.1186/s40168-024-01958-y
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author Hui Liang
Ming Li
Jie Chen
Wenhao Zhou
Dongmei Xia
Qianwen Ding
Yalin Yang
Zhen Zhang
Chao Ran
Zhigang Zhou
author_facet Hui Liang
Ming Li
Jie Chen
Wenhao Zhou
Dongmei Xia
Qianwen Ding
Yalin Yang
Zhen Zhang
Chao Ran
Zhigang Zhou
author_sort Hui Liang
collection DOAJ
description Abstract Background 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. Results 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. Conclusions 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
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spelling doaj-art-00e93a07b5c14974adc0f8ba36c2a4bb2024-11-24T12:35:44ZengBMCMicrobiome2049-26182024-11-0112111610.1186/s40168-024-01958-yThe intestinal microbiome and Cetobacterium somerae inhibit viral infection through TLR2-type I IFN signaling axis in zebrafishHui Liang0Ming Li1Jie Chen2Wenhao Zhou3Dongmei Xia4Qianwen Ding5Yalin Yang6Zhen Zhang7Chao Ran8Zhigang Zhou9Sino-Norway Joint Lab On Fish Gastrointestinal Microbiota, Institute of Feed Research, Chinese Academy of Agricultural SciencesSino-Norway Joint Lab On Fish Gastrointestinal Microbiota, Institute of Feed Research, Chinese Academy of Agricultural SciencesSino-Norway Joint Lab On Fish Gastrointestinal Microbiota, Institute of Feed Research, Chinese Academy of Agricultural SciencesSino-Norway Joint Lab On Fish Gastrointestinal Microbiota, Institute of Feed Research, Chinese Academy of Agricultural SciencesSino-Norway Joint Lab On Fish Gastrointestinal Microbiota, Institute of Feed Research, Chinese Academy of Agricultural SciencesKey Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural SciencesKey Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural SciencesKey Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural SciencesKey Laboratory for Feed Biotechnology of the Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural SciencesSino-Norway Joint Lab On Fish Gastrointestinal Microbiota, Institute of Feed Research, Chinese Academy of Agricultural SciencesAbstract Background 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. Results 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. Conclusions 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 Abstracthttps://doi.org/10.1186/s40168-024-01958-yIntestinal microbiotaAntiviral innate immunityZebrafish
spellingShingle Hui Liang
Ming Li
Jie Chen
Wenhao Zhou
Dongmei Xia
Qianwen Ding
Yalin Yang
Zhen Zhang
Chao Ran
Zhigang Zhou
The intestinal microbiome and Cetobacterium somerae inhibit viral infection through TLR2-type I IFN signaling axis in zebrafish
Microbiome
Intestinal microbiota
Antiviral innate immunity
Zebrafish
title The intestinal microbiome and Cetobacterium somerae inhibit viral infection through TLR2-type I IFN signaling axis in zebrafish
title_full The intestinal microbiome and Cetobacterium somerae inhibit viral infection through TLR2-type I IFN signaling axis in zebrafish
title_fullStr The intestinal microbiome and Cetobacterium somerae inhibit viral infection through TLR2-type I IFN signaling axis in zebrafish
title_full_unstemmed The intestinal microbiome and Cetobacterium somerae inhibit viral infection through TLR2-type I IFN signaling axis in zebrafish
title_short The intestinal microbiome and Cetobacterium somerae inhibit viral infection through TLR2-type I IFN signaling axis in zebrafish
title_sort intestinal microbiome and cetobacterium somerae inhibit viral infection through tlr2 type i ifn signaling axis in zebrafish
topic Intestinal microbiota
Antiviral innate immunity
Zebrafish
url https://doi.org/10.1186/s40168-024-01958-y
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