Ligilactobacillus murinus-derived metabolites 5-hydroxyindole inhibit pseudorabies virus infection via regulation of STING-AhR pathway_RNA-seq

The pseudorabies virus (PRV) is a zoonotic pathogen that circulates among a wide range of animals and is deemed a public health threat. The Stimulator of Interferon Genes (STING) is crucial for innate immunity against DNA viruses and intestinal homeostasis, yet its influence on gut microbiota-mediated antiviral immunity is unclear. Here, we found that STING-KO mice and IFNAR1-KO mice lower the survival rates of PRV infected mice by promoting the increase of pro-inflammatory factors and reducing the number of alveolar macrophages (AMs) in the lung. Furthermore, our results demonstrate that STING-KO mice expressively decreased the abundance of gut Ligilactobacillus murinus (L.murinus) from PRV-infected mice. Moreover, L.murinus and 5-hydroxyindole (5-HI) protect antibiotic (Abx) treatment mice from PRV infection, which induce the activation of aryl hydrocarbon receptor (AhR) in a STING-dependent manner. Collectively, these findings highlight that STING inhibits PRV infection by regulating L.murinus and 5-HI to activate AhR.