한빛사논문
- 조회733
Da Hyun Kim1, Minju Jeong2, Jae Hwan Kim1, Joe Eun Son3, John J. Y. Lee3, Sang-jun Park4, Juyeon Lee4, Minwoo Kim1, Jong-Won Oh1, Myeong Soo Park4, and Sanguine Byun1*
1Department of Biotechnology, Yonsei University, Seoul 03722, Republic of Korea. 2Department of Agricultural Biotechnology, Seoul National University, Seoul 08826, Republic of Korea. 3Program in Developmental and Stem Cell Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 4Research Center, BIFIDO Co. Ltd., Hanam 12930, Republic of Korea
Address correspondence to: SANGUINE BYUN
Abstract
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-α and IFN-β) and tumor necrosis factor-α production in mouse and human macrophages, promoting antiviral innate responses against norovirus infection. Investigation on the molecular mechanism demonstrated that HHuMin-U can activate nuclear factor κB 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-β levels 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.
논문정보
- Research article
- 2022년 12월 (BRIC 등록일 2022-12-22)
- 국내 연구진
- 생명과학 > 식품학
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