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MicroRNA-155 modulates the pathogen binding ability of dendritic cells (DCs) by down-regulation of DC-specific

Rocio T Martinez-Nunez1, Fethi Louafi1, Peter S Friedmann1

  • 1From the Division of Infection, Inflammation and Repair, University of Southampton School of Medicine, Southampton SO16 6YD, United Kingdom.

The Journal of Biological Chemistry
|April 24, 2009
PubMed

Insights

MicroRNA-155 (miR-155) regulates dendritic cell (DC) maturation by targeting PU.1, reducing DC-SIGN expression. This impacts pathogen binding, influencing how infections enter the body.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • MicroRNA-155 (miR-155) is implicated in inflammatory responses.
  • Dendritic cells (DCs) are crucial for initiating adaptive immunity.
  • Pathogen recognition and binding by DCs are key steps in host defense.

Purpose of the Study:

  • To elucidate the role of miR-155 in human dendritic cell maturation.
  • To investigate how miR-155 modulates pathogen binding.
  • To identify the molecular targets of miR-155 in DCs.

Main Methods:

  • Quantitative analysis of miR-155 and PU.1 levels during DC maturation.
  • Luciferase reporter assays to confirm PU.1 as a direct miR-155 target.
  • Overexpression studies in THP1 cells to assess effects on PU.1 and DC-SIGN.
  • Measurement of DC-SIGN mRNA and protein levels.
  • Assessment of pathogen (fungi, HIV gp-120) binding to DCs.

Main Results:

  • miR-155 expression increased significantly (up to 130-fold) during DC maturation, correlating with decreased PU.1 protein.
  • PU.1 was identified as a direct target of miR-155, with the binding site in the 3'-untranslated region.
  • Overexpression of miR-155 reduced PU.1 and DC-SIGN (mRNA and protein) levels.
  • Reduced PU.1 levels correlated with decreased DC-SIGN promoter activity and mRNA expression.
  • Higher miR-155 levels in DCs led to reduced binding capacity for fungi and HIV gp-120.

Conclusions:

  • miR-155 plays a critical role in human DC maturation by down-regulating PU.1.
  • This miR-155-PU.1 axis reduces DC-SIGN expression on the cell membrane.
  • The modulation of DC-SIGN by miR-155 affects pathogen binding, impacting host susceptibility to infections.
  • These findings suggest a novel mechanism for miR-155 in regulating cellular immune responses to pathogens.

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