RESUMEN
We analyzed dendritic cell (DC) and NK cell compartments in relation to CD4 recovery in 21 HIV-infected subjects followed to <50 copies/ml once starting antiretroviral therapy (ART) and observed for 52 wk of sustained suppression. Although CD4 counts increased in all subjects in response to ART, we observed a restoration of functional plasmacytoid DC (PDC) after 52 wk of sustained suppression under ART (from 1850 cells/ml to 4550 cells/ml) to levels comparable to controls (5120 cells/ml) only in subjects with a low baseline viral load, which also rapidly suppressed to <50 copies/ml upon Asunto(s)
Infecciones por VIH/inmunología
, VIH-1
, Inmunidad Innata
, Recuperación de la Función/inmunología
, Carga Viral
, Adulto
, Recuento de Linfocito CD4
, Linfocitos T CD4-Positivos/inmunología
, Células Dendríticas/inmunología
, Femenino
, Estudios de Seguimiento
, Infecciones por VIH/tratamiento farmacológico
, VIH-1/inmunología
, Humanos
, Inmunidad Innata/efectos de los fármacos
, Células Asesinas Naturales/inmunología
, Activación de Linfocitos/efectos de los fármacos
, Activación de Linfocitos/inmunología
, Masculino
, Persona de Mediana Edad
, Células Plasmáticas/inmunología
, Recuperación de la Función/efectos de los fármacos
, Viremia/tratamiento farmacológico
, Viremia/inmunología
RESUMEN
Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) has been described as an attachment molecule for human immunodeficiency virus type 1 (HIV-1) with the potential to mediate its transmission. We examined DC-SIGN expression in monocyte-derived macrophages (MDM) and its role in viral transmission when MDM were exposed to interleukin (IL)-13, IL-4, or interferon-gamma (IFN-gamma). We show that IL-13 and IL-4 increase transcripts, total protein, and cell-surface expression of DC-SIGN in all MDM tested, IFN-gamma results ranged from no change to up-regulation of surface expression, and message and total protein were, respectively, induced in all and 86% of donors tested. Transmission experiments of HIV-1 X4 between cytokine-treated MDM to Sup-T1 cells showed no association between total transmission and DC-SIGN up-regulation. IL-4 but not IL-13 resulted in a less than twofold increase in MDM viral transmission to CD4+ T cells in spite of a fourfold up-regulation in DC-SIGN expression by either cytokine. In contrast, IFN-gamma treatment induced a decrease in total transmission by at least two-thirds, despite its induction of DC-SIGN. Soluble mannan resulted in a greater inhibition of viral transmission to CD4+ T cells than neutralizing anti-DC-SIGN monoclonal antibody (67-75% vs. 39-48%), supporting the role of mannose-binding receptors in viral transmission. Taken together, results show that DC-SIGN regulation in MDM does not singly predict the transmission potential of this cell type.