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<p>Pseudorabies virus (PRV) infects a wide range of mammals and poses a potential threat to human health. The stimulator of interferon genes (STING) is crucial for innate immunity against DNA viruses and intestinal homeostasis; however, its influence on gut microbiota-mediated antiviral immunity is unclear. Here, we demonstrate that deletion of the STING gene or the IFNAR1 gene in mice aggravates PRV-induced lung pathology, increases viral load and inflammatory cytokine expression, reduces type I interferon transcription, and ultimately decreases survival of STING-KO mice and IFNAR1-KO mice. Additionally, STING deficiency causes rapid loss of alveolar macrophages (AMs) in the lungs following PRV infection, promotes neutrophil and monocyte recruitment through activation of inflammation-related signaling pathways, and disrupts the pulmonary immune cell balance. Furthermore, STING-deficient mice exhibit a markedly reduced abundance of <i>Ligilactobacillus murinus</i> (<i>L. murinus</i>) in the gut after PRV infection, and the level of 5-hydroxyindole (5-HI) correlates positively with intestinal <i>Ligilactobacillus</i> abundance. <i>L. murinus</i> modulates gut microbiota-derived 5-hydroxyindole. Moreover, <i>L. murinus</i> and 5-HI protect antibiotic (Abx)-treated mice from PRV infection by activating the aryl hydrocarbon receptor (AhR) in a STING-dependent manner, and this protective effect is abolished in <i>Ahr</i><sup>−</sup><sup><i>/</i></sup><sup>−</sup> mice. Collectively, these findings highlight that STING inhibits PRV infection by regulating L. murinus and 5-HI, which leads to activation of AhR.</p>

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Ligilactobacillus murinus modulates gut microbiota-derived 5-hydroxyindole to inhibit pseudorabies virus infection via activation of the aryl hydrocarbon receptor

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月17日

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  • Man-Jie Hu,
  • Yong-Lei Yang,
  • Ya-Xin Yang,
  • Rong-Rong Zhang,
  • Tian-Kui Guo,
  • Jun-Hong Xing,
  • Bing Liu,
  • M. Azeem Riaz,
  • Ying-Shi Yang,
  • Lin-Jiao Yu,
  • Jing-Yi Pang,
  • Ying Zhao,
  • Chun-Wei Shi,
  • Gui-Lian Yang,
  • Hai-Bin Huang,
  • Yan-Long Jiang,
  • Jian-Zhong Wang,
  • Xin Cao,
  • Nan Wang,
  • Yan Zeng,
  • Wen-Tao Yang,
  • Chun-Feng Wang

摘要

Pseudorabies virus (PRV) infects a wide range of mammals and poses a potential threat to human health. The stimulator of interferon genes (STING) is crucial for innate immunity against DNA viruses and intestinal homeostasis; however, its influence on gut microbiota-mediated antiviral immunity is unclear. Here, we demonstrate that deletion of the STING gene or the IFNAR1 gene in mice aggravates PRV-induced lung pathology, increases viral load and inflammatory cytokine expression, reduces type I interferon transcription, and ultimately decreases survival of STING-KO mice and IFNAR1-KO mice. Additionally, STING deficiency causes rapid loss of alveolar macrophages (AMs) in the lungs following PRV infection, promotes neutrophil and monocyte recruitment through activation of inflammation-related signaling pathways, and disrupts the pulmonary immune cell balance. Furthermore, STING-deficient mice exhibit a markedly reduced abundance of Ligilactobacillus murinus (L. murinus) in the gut after PRV infection, and the level of 5-hydroxyindole (5-HI) correlates positively with intestinal Ligilactobacillus abundance. L. murinus modulates gut microbiota-derived 5-hydroxyindole. Moreover, L. murinus and 5-HI protect antibiotic (Abx)-treated mice from PRV infection by activating the aryl hydrocarbon receptor (AhR) in a STING-dependent manner, and this protective effect is abolished in Ahr−/− mice. Collectively, these findings highlight that STING inhibits PRV infection by regulating L. murinus and 5-HI, which leads to activation of AhR.