title: Impaired CCR7 expression on plasmacytoid dendritic cells of HIV-infected children and adolescents with immunologic and virologic failure.
abstract: BACKGROUND
  Defects of plasmacytoid (p) and myeloid (m) dendritic cells (DCs) occur in HIV infection. The aim of this study was to evaluate the maturation and function of DCs in children with perinatal HIV infection who were on antiretroviral therapy.
  
  
  METHODS
  Twenty HIV-infected children (median age = 12.9 years) classified as immunologic/virologic responders and failures were evaluated in a whole-blood assay with resiquimod (RSQ), a potent agonist to Toll-like receptors 7 and 8, as the DC stimulant.
  
  
  RESULTS
  In comparison to controls, pDC and mDC numbers were decreased in patients, but RSQ stimulation resulted in upregulation of CD83, CD80, and tumor necrosis factor-alpha in both DC subsets and upregulation of interferon (IFN)-alpha in pDCs. Patients with immunologic and virologic failure demonstrated a selective impairment in upregulation of lymph node homing marker CCR7 in pDCs. Plasma virus load was negatively correlated with IFNalpha and CCR7 expression, whereas CD4 percentage correlated only with CCR7 expression in pDCs.
  
  
  CONCLUSIONS
  A novel defect of pDCs, impaired CCR7 upregulation, is described in association with immunologic or virologic failure. This deficiency could impair homing of pDCs to lymph nodes, leading to secondary defects of mDC maturation and poor T-cell activation.
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Desai
authors.forename: Aida
authors.initials: A
authors.lastname: Chaparro
authors.forename: Huanliang
authors.initials: H
authors.lastname: Liu
authors.forename: Patrick
authors.initials: P
authors.lastname: Haslett
authors.forename: Kristopher
authors.initials: K
authors.lastname: Arheart
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Scott
authors.forename: Rajendra
authors.initials: R
authors.lastname: Pahwa
authors.forename: Savita
authors.initials: S
authors.lastname: Pahwa
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D001772:Blood Cell Count; D018791:CD4 Lymphocyte Count; D002478:Cells, Cultured; D002648:Child; D003713:Dendritic Cells / Q000378:metabolism*; D005434:Flow Cytometry; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007136:Immunoglobulins / Q000378:metabolism; D016898:Interferon-alpha / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism*; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D019562:Viral Load; D000097802:CD83 Antigen
chemical_list: D044966:Anti-Retroviral Agents; D015703:Antigens, CD; D018122:B7-1 Antigen; D007093:Imidazoles; D007136:Immunoglobulins; D016898:Interferon-alpha; D008562:Membrane Glycoproteins; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D000097802:CD83 Antigen; C515370:CCR7 protein, human; C402365:resiquimod