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Lactobacillus salivarius HHuMin-U Activates Innate Immune Defense against Norovirus Infection through TBK1-IRF3 and NF-κB Signaling Pathways

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Research 2023年第3期2022卷 229-241页

作者： Da Hyun Kim Minju Jeong Jae Hwan Kim Joe Eun Son john jylee Sang-jun Park Juyeon Lee Minwoo Kim Jong-Won Oh Myeong Soo Park Sanguine Byun Department of Biotechnology Yonsei UniversitySeoul 03722Republic of Korea Department of Agricultural Biotechnology Seoul National UniversitySeoul 08826Republic of Korea Program in Developmental and Stem Cell Biology The Hospital for Sick ChildrenTorontoOntarioCanada Research Center BIFIDO Co.Ltd.Hanam 12930Republic of Korea

The composition of commensal bacteria plays a critical role in controlling immune responses in the *** have shown that specific bacterial strains may have the capacity to enhance host immune defense against gastrointestinal viral *** norovirus is known to be the most common cause of gastroenteritis,leading to an estimated 200,000 deaths every year,identification of bacterial strains with protective effects against norovirus infection remains ***,we discovered Lactobacillus salivarius HHuMin-U(HHuMin-U)as a potent antiviral strain against norovirus ***-U significantly suppressed murine norovirus replication and lowered viral RNA titers in *** transcriptome sequencing(RNA sequencing)analysis revealed that HHuMin-U markedly enhanced the expression level of antiviral interferon-stimulated genes compared to mock ***-U treatment dose-dependently induced type I interferons(IFN-αand IFN-β)and tumor necrosis factor-αproduction in mouse and human macrophages,promoting antiviral innate responses against norovirus *** on the molecular mechanism demonstrated that HHuMin-U can activate nuclear factorκB and TANK-binding kinase 1(TBK1)–interferon regulatory factor 3 signaling pathways,leading to the phosphorylation of signal transducer and activator of transcription 1 and signal transducer and activator of transcription 2,the key mediators of interferon-stimulated ***,oral administration of HHuMin-U increased IFN-βlevels in the ileum of mice and altered the gut microbiome *** results suggest the species/strain-specific importance of gut microbial composition for antiviral immune responses and the potential use of HHuMin-U as a probiotic agent.

关键词： TBK1 interferon protective

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