Impaired CCR7 expression on plasmacytoid dendritic cells of HIV-infected children and adolescents with immunologic and virologic failure

Background: Defects of plasmacytoid (p) and myeloid (in) 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. Materials and 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-a 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 IFN alpha 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.