Unraveling the functions of plasmacytoid dendritic cells during viral infections, autoimmunity, and tolerance

Immunol Rev. 2010 Mar;234(1):142-62. doi: 10.1111/j.0105-2896.2009.00881.x.


Plasmacytoid dendritic cells (pDCs) are bone marrow-derived cells that secrete large amounts of type I interferon (IFN) in response to viruses. Type I IFNs are pleiotropic cytokines with antiviral activity that also enhance innate and adaptive immune responses. Viruses trigger activation of pDCs and type I IFN responses mainly through the Toll-like receptor pathway. However, a variety of activating and inhibitory pDC receptors fine tune the amplitude of type I IFN responses. Chronic activation and secretion of type I IFN in the absence of infection can promote autoimmune diseases. Furthermore, while activated pDCs promote immunity and autoimmunity, resting or alternatively activated pDCs may be tolerogenic. The various roles of pDCs have been extensively studied in vitro and in vivo with depleting antibodies. However, depleting antibodies cross-react with other cell types that are critical for eliciting protective immunity, potentially yielding ambiguous phenotypes. Here we discuss new approaches to assess pDC functions in vivo and provide preliminary data on their potential roles during viral infections. Such approaches would also prove useful in the more specific evaluation of how pDCs mediate tolerance and autoimmunity. Finally, we discuss the emergent role of pDCs and one of their receptors, tetherin, in human immunodeficiency virus pathogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antigens, CD / immunology
  • Autoimmunity*
  • CD8-Positive T-Lymphocytes / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / virology
  • GPI-Linked Proteins
  • HIV / immunology
  • HIV / pathogenicity
  • HIV Infections / immunology
  • HIV Infections / virology
  • Humans
  • Immune Tolerance*
  • Immunity, Innate
  • Interferon Type I / immunology
  • Membrane Glycoproteins / immunology
  • Mice
  • Receptors, Immunologic / immunology
  • Signal Transduction
  • Virus Diseases / immunology*
  • Virus Diseases / virology


  • Antigens, CD
  • BST2 protein, human
  • GPI-Linked Proteins
  • Interferon Type I
  • Membrane Glycoproteins
  • Receptors, Immunologic