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Responsiveness of fibrocytes to toll-like receptor danger signals

Carole Balmelli1, Marco P Alves, Esther Steiner

  • 1Institute of Virology and Immunoprophylaxis, Sensemattstrasse 293, CH-3147, Mittelhäusern, Switzerland. Carole.Balmelli@ivi.admin.ch

Immunobiology
|December 19, 2007
PubMed

Insights

Fibrocytes, a type of myeloid cell, are potent responders to toll-like receptor (TLR) danger signals, producing high levels of interleukin-6 and type I interferon upon viral stimulation. This suggests fibrocytes play a key role in the innate immune system

Area of Science:

  • Immunology
  • Cell Biology
  • Innate Immunity

Background:

  • Circulating myeloid cells, including plasmacytoid dendritic cells (pDCs), blood dendritic cells (DCs), and monocytes, function as sentinels of the innate immune system.
  • These cells detect pathogens via Toll-like Receptors (TLRs), initiating immune responses.
  • Fibrocytes are a less-studied blood-derived myeloid cell type.

Purpose of the Study:

  • To investigate the Toll-like Receptor (TLR) responsiveness of fibrocytes.
  • To compare fibrocyte immune activation to other myeloid cells like pDCs and DCs.
  • To explore the role of fibrocytes in the initial defense against pathogens.

Main Methods:

  • Analysis of fibrocyte response to various TLR ligands (TLR2, TLR4, TLR7) and viral stimulation.
  • Quantification of interleukin-6 (IL-6) production and Type I Interferon (IFN) induction.
  • Assessment of NF-kappaB transcription factor translocation.
  • Flow cytometry analysis of TLR7 expression in peripheral blood leukocyte subpopulations, including fibrocyte precursors.

Main Results:

  • Fibrocytes demonstrated robust responses to TLR2, TLR4, and TLR7 ligands, as well as poly (I:C) and viral stimulation.
  • Fibrocytes produced significantly higher amounts of IL-6 compared to pDCs (5-fold) and Flt3 ligand-derived DCs (60-fold).
  • Viral infection of fibrocytes induced Type I Interferon (IFN) production.
  • A rapid and efficient translocation of the NF-kappaB transcription factor was observed in activated fibrocytes.
  • TLR7 was found to be expressed and functional in a CD163(+) monocytic cell subpopulation containing fibrocyte precursors.

Conclusions:

  • Fibrocytes exhibit potent immune activation capabilities, particularly in response to TLR ligands and viral stimuli.
  • Their high production of IL-6 and IFN suggests a significant role in innate immunity, potentially exceeding that of pDCs and DCs in certain contexts.
  • The findings highlight the importance of fibrocytes as first-line defenders against pathogen invasion, especially following trauma.
  • Fibrocyte precursors express functional TLR7, indicating a specific mechanism for pathogen detection.

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