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Filamentous bacteriophage M13 induces proinflammatory responses in intestinal epithelial cells

Ambarish C Varadan1,2, Juris A Grasis1,2

  • 1Department of Molecular and Cellular Biology, University of California, Merced, California, USA.

Infection and Immunity
|April 10, 2025
PubMed

Insights

Filamentous bacteriophages, like M13, directly impact intestinal epithelial cells, influencing immune responses and potentially contributing to gut health and disease. This research highlights their role in intestinal inflammation.

Area of Science:

  • Microbiology
  • Immunology
  • Gastroenterology

Background:

  • Bacteriophages are abundant in the human gut microbiome.
  • Specific bacteriophage populations are altered in inflammatory bowel diseases (IBD) like Crohn's disease (CD) and ulcerative colitis (UC).
  • The direct impact of bacteriophages on intestinal epithelial cells and inflammation remains unclear.

Purpose of the Study:

  • To investigate the hypothesis that a high bacteriophage burden directly induces intestinal epithelial responses.
  • To compare the effects of filamentous bacteriophages (M13, Fd) versus lytic bacteriophages (T4, ϕX174) on intestinal epithelial cells.
  • To elucidate the mechanisms by which bacteriophages modulate antiviral and antimicrobial responses.

Main Methods:

  • Treatment of human intestinal epithelial cell line (HT-29) with different bacteriophages.
  • Measurement of Interleukin-8 (IL-8) expression.
  • Assessment of bacterial internalization into HT-29 cells.
  • Analysis of Type I and III Interferon (IFN) and LL-37 expression.

Main Results:

  • Filamentous bacteriophages M13 and Fd induced dose-dependent IL-8 expression in HT-29 cells.
  • M13, but not Fd, reduced bacterial internalization in HT-29 cells.
  • M13 upregulated Type I and III IFN expressions and augmented short-chain fatty acid (SCFA)-mediated LL-37 expression.

Conclusions:

  • Filamentous bacteriophages directly influence human intestinal epithelial cells.
  • These interactions involve modulation of immune responses, including IFN and LL-37 expression.
  • Findings provide insights into bacteriophage-mucosa interactions relevant to intestinal disease pathogenesis.
Keywords:
FdM13bacteriophageenteric viromefilamentous bacteriophageinovirusintestinal epithelial cells (IECs)

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