Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway
Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway
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DOI：
10.1038/s41598-019-44263-7
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发表时间：
2019-05-27
影响因子：
4.6
通讯作者：
McKeating, Jane A.
中科院分区：
文献类型：
--
作者：
Benedikz, Elizabeth K.;Bailey, Dalan;McKeating, Jane A.
病毒和细菌通过侵入上皮屏障来定殖宿主。最近的研究表明，微生物群，病原体和宿主之间的相互作用可以通过知之甚少的机制加强感染。在这里，我们研究了不同的细菌物种是否可以调节病毒内化到宿主细胞中，这通常是建立感染的限速步骤。表达流感、麻疹、埃博拉、拉沙或水疱性口炎病毒包膜糖蛋白的慢病毒假病毒使我们能够研究利用不同内化途径的病毒的进入。鼠伤寒沙门氏菌，大肠杆菌和铜绿假单胞菌显着增加病毒摄取，即使在低细菌频率。这不需要细菌接触或侵入宿主细胞。研究确定负责这种前病毒活性的细菌抗原是Toll样受体5（TLR 5）激动剂鞭毛蛋白。暴露于鞭毛蛋白以温度依赖性方式通过TLR 5依赖性激活NF-κ B增加病毒对上皮细胞的附着。重要的是，这种表型是持久的，并且在低感染复数下可检测到。鞭毛蛋白从细菌中脱落，我们的研究揭示了这种蛋白质在调节病毒进入中的新的旁观者作用。这突出了病毒-细菌相互作用的一个新方面，对我们理解多种微生物相关的发病机制具有重要意义。
Viruses and bacteria colonize hosts by invading epithelial barriers. Recent studies have shown that interactions between the microbiota, pathogens and the host can potentiate infection through poorly understood mechanisms. Here, we investigated whether diverse bacterial species could modulate virus internalization into host cells, often a rate-limiting step in establishing infections. Lentiviral pseudoviruses expressing influenza, measles, Ebola, Lassa or vesicular stomatitis virus envelope glycoproteins enabled us to study entry of viruses that exploit diverse internalization pathways. Salmonella Typhimurium, Escherichia coli and Pseudomonas aeruginosa significantly increased viral uptake, even at low bacterial frequencies. This did not require bacterial contact with or invasion of host cells. Studies determined that the bacterial antigen responsible for this pro-viral activity was the Toll-Like Receptor 5 (TLR5) agonist flagellin. Exposure to flagellin increased virus attachment to epithelial cells in a temperature-dependent manner via TLR5-dependent activation of NF-KB. Importantly, this phenotype was both long lasting and detectable at low multiplicities of infection. Flagellin is shed from bacteria and our studies uncover a new bystander role for this protein in regulating virus entry. This highlights a new aspect of viral-bacterial interplay with significant implications for our understanding of polymicrobial-associated pathogenesis.