Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway

Sci Rep. 2019 May 27;9(1):7903. doi: 10.1038/s41598-019-44263-7.


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-ΚB. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Antigens, Bacterial / metabolism*
  • Bacterial Infections / immunology
  • Bacterial Infections / microbiology
  • Coinfection / immunology*
  • Coinfection / microbiology
  • Disease Susceptibility / immunology
  • Disease Susceptibility / microbiology
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Flagellin / metabolism*
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Host Microbial Interactions / immunology*
  • Humans
  • Lung / cytology
  • Permeability
  • RNA, Small Interfering / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Toll-Like Receptor 5 / agonists
  • Toll-Like Receptor 5 / metabolism
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • Virus Diseases / immunology
  • Virus Diseases / virology
  • Virus Internalization*


  • Antigens, Bacterial
  • RELA protein, human
  • RNA, Small Interfering
  • TLR5 protein, human
  • Toll-Like Receptor 5
  • Transcription Factor RelA
  • Flagellin