Responsiveness of fibrocytes to toll-like receptor danger signals.
Circulating myeloid cells such as plasmacytoid dendritic cells (pDC), blood DC and monocytes act as blood sentinels detecting invading pathogens through a large repertoire of expression of toll-like receptors (TLRs). Activation of these receptors is crucial to detect invading pathogens by the innate immune system. In the present work, we analysed the TLR responsiveness of fibrocytes, a blood-derived cell type of myeloid origin. Fibrocytes efficiently responded to TLR2, TLR4, and TLR7 ligands as well as to poly (I:C) or viral stimulation by producing high amount of interleukin-6. Upon virus infection of fibrocytes, IFN type I was also induced. When compared to pDC or Flt3 ligand-derived DC, fibrocytes produced 5 times and 60 times more IL-6, respectively. This response was associated with a rapid and efficient translocation of the NF-kappaB transcription factor. Analysis of the expression and functionality of TLR7 in peripheral blood leukocyte subpopulations suggested that this receptor is expressed and functional in a CD163(+) monocytic cell subpopulation containing the fibrocyte precursors. Considering the rapid entry of fibrocytes into wounds, this efficient responsiveness to TLR danger signals, reflects a potentially important role of these cells in the first line of defence against pathogen invasion following traumata.
Balmelli
Carole
C
Institute of Virology and Immunoprophylaxis, Sensemattstrasse 293, CH-3147, Mittelhäusern, Switzerland. Carole.Balmelli@ivi.admin.ch
Alves
Marco P
MP
Steiner
Esther
E
Zingg
Daniel
D
Peduto
Nadja
N
Ruggli
Nicolas
N
Gerber
Heidi
H
McCullough
Kenneth
K
Summerfield
Artur
A
D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007369:Interferon Inducers / Q000494:pharmacology; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D011070:Poly I-C / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism*; D000098902:CD163 Antigen
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D016207:Cytokines; D007369:Interferon Inducers; D016898:Interferon-alpha; D015850:Interleukin-6; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D011070:Poly I-C