Interferon-producing cells: on the front line in immune responses against pathogens.

Interferon-producing cells (IPC) constitute a small population of leukocytes that secrete high levels of type I interferons in response to viruses. Although human IPC have been known for almost two decades, murine IPC have been identified only recently. Furthermore, it has been shown that IPC correspond to the enigmatic 'plasmacytoid cells' identified in human lymph nodes during infections. These breakthroughs have brought IPC to the attention of immunologists for their role in innate immunity and in shaping T cell responses. Here we review recent progress and outstanding questions in the field.

[1]  G. Trinchieri,et al.  Human thymus contains IFN-alpha-producing CD11c(-), myeloid CD11c(+), and mature interdigitating dendritic cells. , 2001, The Journal of clinical investigation.

[2]  F. Lund-Johansen,et al.  Dendritic cell ontogeny: a human dendritic cell lineage of myeloid origin. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[3]  L. Adorini,et al.  Cutting Edge: Selective Usage of Chemokine Receptors by Plasmacytoid Dendritic Cells1 , 2001, The Journal of Immunology.

[4]  J. Banchereau,et al.  The Enigmatic Plasmacytoid T Cells Develop into Dendritic Cells with Interleukin (IL)-3 and CD40-Ligand , 1997, The Journal of experimental medicine.

[5]  L. Rönnblom,et al.  Patients with systemic lupus erythematosus (SLE) have a circulating inducer of interferon‐alpha (IFN‐α) production acting on leucocytes resembling immature dendritic cells , 1999, Clinical and experimental immunology.

[6]  S. Akira,et al.  Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[7]  N. Kadowaki,et al.  The nature of the principal type 1 interferon-producing cells in human blood. , 1999, Science.

[8]  Virginia Pascual,et al.  Induction of Dendritic Cell Differentiation by IFN-α in Systemic Lupus Erythematosus , 2001, Science.

[9]  A. Lanzavecchia,et al.  Mouse pre‐immunocytes as non‐proliferating multipotent precursors of macrophages, interferon‐producing cells, CD8α+ and CD8α– dendritic cells , 2001 .

[10]  S. Heimfeld,et al.  Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells. , 2000, Blood.

[11]  U. Ramstedt,et al.  Properties of human natural interferon‐producing cells stimulated by tumor cell lines , 1983, European journal of immunology.

[12]  P Björck,et al.  Isolation and characterization of plasmacytoid dendritic cells from Flt3 ligand and granulocyte-macrophage colony-stimulating factor-treated mice. , 2001, Blood.

[13]  M. Colonna,et al.  Virus-induced Interferon α Production by a Dendritic Cell Subset in the Absence of Feedback Signaling In Vivo , 2002, The Journal of experimental medicine.

[14]  B. Blom,et al.  Generation of Interferon α–Producing Predendritic Cell (Pre-Dc)2 from Human Cd34+ Hematopoietic Stem Cells , 2000, The Journal of experimental medicine.

[15]  C. Maliszewski,et al.  Plasmacytoid monocytes/T cells: a dendritic cell lineage? , 2001, Seminars in immunology.

[16]  B. Pulendran,et al.  Distinct dendritic cell subsets differentially regulate the class of immune response in vivo. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[17]  R. Gressin,et al.  Identification of a leukemic counterpart of the plasmacytoid dendritic cells. , 2001, Blood.

[18]  P. Fitzgerald-Bocarsly.  Human natural interferon-α producing cells , 1993, Pharmacology & Therapeutics.

[19]  K. Lennert,et al.  Plasmacytoid T-cell clusters in non-specific lymphadenitis , 1983, Virchows Archiv. B, Cell pathology including molecular pathology.

[20]  Y. Belkaid,et al.  The Role of Interleukin (IL)-10 in the Persistence of Leishmania major in the Skin after Healing and the Therapeutic Potential of Anti–IL-10 Receptor Antibody for Sterile Cure , 2001, The Journal of experimental medicine.

[21]  I. Weissman,et al.  Cell-fate conversion of lymphoid-committed progenitors by instructive actions of cytokines , 2000, Nature.

[22]  B. Gazzard,et al.  Loss of blood CD11c(+) myeloid and CD11c(-) plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load. , 2001, Blood.

[23]  Antonio Lanzavecchia,et al.  BDCA-2, a Novel Plasmacytoid Dendritic Cell–specific Type II C-type Lectin, Mediates Antigen Capture and Is a Potent Inhibitor of Interferon α/β Induction , 2001, The Journal of experimental medicine.

[24]  G. Trinchieri,et al.  Persistent Decreases in Blood Plasmacytoid Dendritic Cell Number and Function Despite Effective Highly Active Antiretroviral Therapy and Increased Blood Myeloid Dendritic Cells in HIV-Infected Individuals1 , 2002, The Journal of Immunology.

[25]  N. Harris,et al.  Plasmacytoid T-zone cell proliferation in a patient with chronic myelomonocytic leukemia. Histologic and immunohistologic characterization. , 1991, The American journal of surgical pathology.

[26]  N. Kadowaki,et al.  Natural Interferon α/β–Producing Cells Link Innate and Adaptive Immunity , 2000, The Journal of experimental medicine.

[27]  B. Blom,et al.  Introduction: TH2-inducing DC2 for immunotherapy. , 2000, Blood.

[28]  S. Akira,et al.  A Toll-like receptor recognizes bacterial DNA , 2000, Nature.

[29]  F. Gheyas,et al.  Depletion of circulating natural type 1 interferon-producing cells in HIV-infected AIDS patients. , 2001, Blood.

[30]  N. Kadowaki,et al.  Subsets of Human Dendritic Cell Precursors Express Different Toll-like Receptors and Respond to Different Microbial Antigens , 2001, The Journal of experimental medicine.

[31]  V. Hornung,et al.  Identification of CpG oligonucleotide sequences with high induction of IFN‐α/β in plasmacytoid dendritic cells , 2001 .

[32]  T. Curiel,et al.  Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells , 2001, Nature Medicine.

[33]  P. Fitzgerald-Bocarsly,et al.  Interferon-alpha generation and immune reconstitution during antiretroviral therapy for human immunodeficiency virus infection. , 2001, AIDS.

[34]  T. Giese,et al.  Toll‐like receptor expression reveals CpG DNA as a unique microbial stimulus for plasmacytoid dendritic cells which synergizes with CD40 ligand to induce high amounts of IL‐12 , 2001 .

[35]  G. Trinchieri,et al.  Interferon / and Interleukin 12 Responses to Viral Infections: Pathways Regulating Dendritic Cell Cytokine Expression In Vivo , 2002 .

[36]  T. Curiel,et al.  Reciprocal regulation of plasmacytoid dendritic cells and monocytes during viral infection , 2001, European journal of immunology.

[37]  Ruslan Medzhitov,et al.  Toll-like receptors and innate immunity , 2001, Nature Reviews Immunology.

[38]  P. Ricciardi-Castagnoli,et al.  Production of Interferon‐α/β by Murine Dendritic Cell Lines Stimulated by Virus and Bacteria , 1997, Scandinavian journal of immunology.

[39]  N. Kadowaki,et al.  Reciprocal control of T helper cell and dendritic cell differentiation. , 1999, Science.

[40]  G. Trinchieri,et al.  The Development of Murine Plasmacytoid Dendritic Cell Precursors Is Differentially Regulated by FLT3-ligand and Granulocyte/Macrophage Colony-Stimulating Factor , 2002, The Journal of experimental medicine.

[41]  F. Lund-Johansen,et al.  Experimentally Induced Recruitment of Plasmacytoid (CD123high) Dendritic Cells in Human Nasal Allergy1 , 2000, The Journal of Immunology.

[42]  V. Desmet,et al.  Plasmacytoid T cells. Immunohistochemical evidence for their monocyte/macrophage origin. , 1988, The American journal of pathology.

[43]  Antonio Lanzavecchia,et al.  Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells , 2001, European journal of immunology.

[44]  P. Ricciardi-Castagnoli,et al.  Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. , 1998, Science.

[45]  Marc Dalod,et al.  Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology , 2001, Nature Immunology.

[46]  F. Belardelli,et al.  Type i interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. , 2001, Immunity.

[47]  A. Bakker,et al.  Stem Cells into Predendritic Cell (Pre-DC)2 but Not into Pre-DC1: Evidence for a Lymphoid Origin of Pre-DC2 , 2000 .

[48]  Hanno Langen,et al.  Maturation, Activation, and Protection of Dendritic Cells Induced by Double-stranded RNA , 1999, The Journal of experimental medicine.

[49]  H. Degreef,et al.  Plasmacytoid Monocytes in Jessner's Lymphocytic Infiltration of the Skin , 1990, The American Journal of dermatopathology.

[50]  L. Rönnblom,et al.  Anti-double-stranded DNA antibodies and immunostimulatory plasmid DNA in combination mimic the endogenous IFN-alpha inducer in systemic lupus erythematosus. , 1999, Journal of immunology.

[51]  D. Jarrossay,et al.  Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon , 1999, Nature Medicine.

[52]  L. Rönnblom,et al.  Patients with systemic lupus erythematosus have reduced numbers of circulating natural interferon-alpha- producing cells. , 1998, Journal of autoimmunity.

[53]  L. Rönnblom,et al.  An etiopathogenic role for the type I IFN system in SLE. , 2001, Trends in immunology.

[54]  J. Ellwart,et al.  Bacterial CpG-DNA Triggers Activation and Maturation of Human CD11c−, CD123+ Dendritic Cells1 , 2001, The Journal of Immunology.

[55]  G. Trinchieri.  Regulatory Role of T Cells Producing both Interferon γ and Interleukin 10 in Persistent Infection , 2001, The Journal of experimental medicine.

[56]  G. Hartmann,et al.  CpG DNA: a potent signal for growth, activation, and maturation of human dendritic cells. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[57]  J. Gilmour,et al.  Plasmacytoid Dendritic Cells Are Highly Susceptible to Human Immunodeficiency Virus Type 1 Infection and Release Infectious Virus , 2001, Journal of Virology.

[58]  V. Soumelis,et al.  Dendritic cell lineage, plasticity and cross-regulation , 2001, Nature Immunology.

[59]  G. Trinchieri,et al.  A leukocyte subset bearing HLA-DR antigens is responsible for in vitro alpha interferon production in response to viruses. , 1985, Natural immunity and cell growth regulation.

[60]  R. Flavell,et al.  Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3 , 2001, Nature.

[61]  N. Kadowaki,et al.  Distinct CpG DNA and Polyinosinic-Polycytidylic Acid Double-Stranded RNA, Respectively, Stimulate CD11c− Type 2 Dendritic Cell Precursors and CD11c+ Dendritic Cells to Produce Type I IFN1 , 2001, The Journal of Immunology.

[62]  S. Akira,et al.  Toll-like receptors: critical proteins linking innate and acquired immunity , 2001, Nature Immunology.

[63]  M. Gilliet,et al.  Generation of Human CD8 T Regulatory Cells by CD40 Ligand–activated Plasmacytoid Dendritic Cells , 2002, The Journal of experimental medicine.

[64]  F. Lund-Johansen,et al.  Plasmacytoid dendritic cells (natural interferon- alpha/beta-producing cells) accumulate in cutaneous lupus erythematosus lesions. , 2001, The American journal of pathology.

[65]  M. Gunn,et al.  Cd11c+B220+Gr-1+ Cells in Mouse Lymph Nodes and Spleen Display Characteristics of Plasmacytoid Dendritic Cells , 2001, The Journal of experimental medicine.

[66]  J. Banchereau,et al.  Flt3-Ligand and Granulocyte Colony-Stimulating Factor Mobilize Distinct Human Dendritic Cell Subsets In Vivo1 , 2000, The Journal of Immunology.

[67]  V. Desmet,et al.  Leukemia‐Associated Lymph Node Infiltrates of Plasmacytoid Monocytes (So‐called Plasmacytoid T‐cells) Evidence for Two Distinct Histological and Immunophenotypical Patterns , 1990, The American journal of surgical pathology.

[68]  P. Fitzgerald-Bocarsly,et al.  Decreased interferon-alpha production in HIV-infected patients correlates with numerical and functional deficiencies in circulating type 2 dendritic cell precursors. , 2001, Clinical immunology.

[69]  S. Akira,et al.  Small anti-viral compounds activate immune cells via the TLR7 MyD88–dependent signaling pathway , 2002, Nature Immunology.

[70]  A. Lanzavecchia,et al.  Plasmacytoid dendritic cells activated by influenza virus and CD40L drive a potent TH1 polarization , 2000, Nature Immunology.