Abnormal Cytokine Production by Circulating Monocytes and Dendritic Cells of Myeloid Origin in ART-Treated HIV-1+ Patients Relates to CD4+ T-Cell Recovery and HCV Co-Infection

Maria      Almeida; Miguel      Cordero; Julia      Almeida; Alberto      Orfao

Abstract

HIV-1 infection is associated with dysregulation of cytokine production by peripheral blood (PB) monocytes and dendritic cells (DC), but controversial results have been reported. We aimed to analyze the effect of antiretroviral therapy (ART) on the in vitro production of inflammatory cytokines by PB-stimulated monocytes and DC of myeloid origin -CD33high+ myeloid DC (mDC) and CD33+/CD14-/dim+/CD16high+ DC- from HIV-1+ patients and its relationship with CD4+ T-cell recovery and co-infection with hepatitis C virus (HCV). In vitro cytokine production was analyzed at the single cell level in 32 HIV-1+ patients, grouped according to the number of CD4+ T-cells/μl in PB ( < 200 CD4 versus > 200 CD4). Patients were tested prior to therapy and at weeks +2, +4, +8, +12 and +52 after ART. Prior to ART, production of IL-6, TNF-α and IL-12 by mDC and of IL-8 and IL-12 by CD16+ DC was significantly increased among > 200 CD4 patients. After one year of ART, increased production of IL-8 by monocytes, of TNF-α by mDC and of IL-1β, IL-6 and TNF-α by CD16+ DC was specifically observed among < 200 CD4 HIV-1+ individuals showing a high recovery of PB CD4+ T-cell counts. In turn, we found that the significantly reduced percentage of IL-1β, IL-6, IL-8 and TNF-α-producing monocytes and of IL-6 and IL-8-producing mDC and CD16+ DC, as well as the significantly diminished mean amount of IL-6 produced per monocyte, mDC and CD16+ DC and of IL-12 produced per CD16+ DC observed at week +52 for the > 200 CD4 patients, were related to the presence of coinfection with HCV. In summary, HIV-1+ individuals show abnormal production of inflammatory cytokines by PB-stimulated monocytes and DC of myeloid origin even after one year of ART, such abnormalities being associated with the degree of recovery of PB CD4+ T-cell counts in more immunocompromised patients and HCV co-infection in more immunocompetent HIV-1+ individuals.

Keywords: Dendritic cells, inflammatory cytokines, HIV-1 infection, antiretroviral therapy, CD4+ T-cell recovery, HCV co-infection

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