title: Dendritic cells in innate immune responses against HIV.
abstract: Dendritic cells (DCs) were recently found to be innate immunity effectors against tumoral cells and viruses. (i) In response to most viruses, including HIV, plasmacytoid DCs are responsible for most of the type I IFN secretion, which is strongly anti-viral and induces TH1 type responses. Myeloid DCs secrete IL-12, which is also important for TH1-type and cytotoxic responses. In HIV patient blood, both DC population numbers decrease as early as the primary stage. Plasmacytoid DC numbers correlate with type I IFN secretion, which is a prognosis predictor, particularly under treatment. IL-12 secretion is also defective. Immunotherapies to replace the defective cytokines or to restore a potentially defective DC-T lymphocyte feed-back might help patients restore their immune responses under antiviral therapy. (ii) After measles and other viral infections, or incubation with dsRNA, DCs become cytotoxic and consequently exhibit natural killer function, through upregulation of type I IFN secretion which enhances TRAIL expression. In HIV infection, this mechanism was not demonstrated yet, but it might a) be responsible for the massive apoptosis of uninfected lymphocytes, and b) increase specific immunity through cross-presentation of antigens from infected cells killed by DCs. (iii) DCs direct expansion and effector functions of NK cells in the absence of adaptive-type cytokines and modulate NKT cell IFN-gamma production. Reciprocally, NK activation triggers DC maturation. HIV-1 Tat inhibits NK cell cytotoxicity directly and probably through inhibition of IL-12 secretion by DC. Therefore, understanding the functions of DCs in innate immune responses and in pathogenesis will help obtain better HIV replication control.
authors.affiliation: Immunobiologie Fondamentale et Clinique, CERVI-INSERM U503, 21 avenue Tony Garnier, 69007 Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Servet
authors.forename: L
authors.initials: L
authors.lastname: Zitvogel
authors.forename: A
authors.initials: A
authors.lastname: Hosmalin
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy; D000818:Animals; D017951:Antigen Presentation; D018952:Antigens, CD34 / Q000096:biosynthesis; D051017:Apoptosis Regulatory Proteins; D019013:CD40 Antigens / Q000096:biosynthesis; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D006678:HIV / Q000378:metabolism*; D015658:HIV Infections; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008954:Models, Biological; D009447:Neuroblastoma / Q000628:therapy; D013601:T-Lymphocytes / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D018417:Th1 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D018952:Antigens, CD34; D051017:Apoptosis Regulatory Proteins; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12