The composition of commensal bacteria plays a critical role in controlling immune responses in the intestine.Studies have shown that specific bacterial strains may have the capacity to enhance host immune defense agai...The composition of commensal bacteria plays a critical role in controlling immune responses in the intestine.Studies have shown that specific bacterial strains may have the capacity to enhance host immune defense against gastrointestinal viral infections.While 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 elusive.Here,we discovered Lactobacillus salivarius HHuMin-U(HHuMin-U)as a potent antiviral strain against norovirus infection.HHuMin-U significantly suppressed murine norovirus replication and lowered viral RNA titers in macrophages.The transcriptome sequencing(RNA sequencing)analysis revealed that HHuMin-U markedly enhanced the expression level of antiviral interferon-stimulated genes compared to mock treatment.HHuMin-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 infection.Investigation 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 genes.Finally,oral administration of HHuMin-U increased IFN-βlevels in the ileum of mice and altered the gut microbiome profile.These 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.展开更多
基金a National Research Foundation of Korea(NRF)grant funded by the Korean Government(Ministry of Science,ICT and Future Planning)(2020R1A2C1010703).
文摘The composition of commensal bacteria plays a critical role in controlling immune responses in the intestine.Studies have shown that specific bacterial strains may have the capacity to enhance host immune defense against gastrointestinal viral infections.While 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 elusive.Here,we discovered Lactobacillus salivarius HHuMin-U(HHuMin-U)as a potent antiviral strain against norovirus infection.HHuMin-U significantly suppressed murine norovirus replication and lowered viral RNA titers in macrophages.The transcriptome sequencing(RNA sequencing)analysis revealed that HHuMin-U markedly enhanced the expression level of antiviral interferon-stimulated genes compared to mock treatment.HHuMin-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 infection.Investigation 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 genes.Finally,oral administration of HHuMin-U increased IFN-βlevels in the ileum of mice and altered the gut microbiome profile.These 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.
