Blood Myeloid Dendritic Cells and slanDC in Antiretroviral Therapy- Suppressed HIV-Infected Patients

Abstract

Myeloid dendritic cells (mDCs) play a complex role in HIV infection regardless of viral replication. The aim of our study was to analyse mDCs in long term antiretroviral therapy (ART)- suppressed HIV-infected patients. We evaluated the numbers of mDCs and slanDC in the context of different degree of CD4+ T cell recovery, persistent T cell activation (as HLA-DR+/CD3+ expression) and monocyte-macrophage activation assessed in terms of circulating levels of both sCD14 and sCD163. We enrolled 72 aviremic patients under effective ART and 34 healthy donors (HD). Patients were divided into two groups on the bases of ΔCD4, indicating the difference between the value of CD4 at the time of sampling and CD4 nadir. Higher levels of mDCs and slanDC were found in patients with ΔCD4>200/mmc in comparison to HD. In those patients also an increased level of sCD14 was found, whereas sCD163 seemed to be at normal levels. An augmentation of activated CD4 T lymphocytes was found, although less pronounced in patients with ΔCD4<200/mmc. In conclusion, our findings showed an expansion of mDCs with a shift to inflammatory slanDC that could sustain both microbial translocation and HIV latency in CD4 T cells.

Impact of IFN-Free and IFN-Based Treatment on Blood Myeloid Dendritic Cell, Monocyte, Slan-DC, and Activated T Lymphocyte Dynamics during HCV Infection

“…Mascia et al recently [8] described how monocyte-derived cytokines such as CXCL-10 and sCD14 are increased in all stages of fibrosis, underlying the presence of immune activation from F0 to F4 [8,33]. Slan-DCs seem to contribute to the pathogenesis of chronic inflammatory diseases such as Crohn's disease, rheumatoid arthritis, psoriasis, and HIV since they infiltrate the inflamed ileal mucosa, skin, and synovial tissue [16,28,34]. They are a major source of tumor necrosis factor-α, a pleiotropic cytokine produced even by macrophages/monocytes in response to bacterial LPS, and are significantly expanded in patients with bacterial sepsis [34].…”

“…To enumerate DCs and monocytes, the same staining protocols previously described by our research group have been used [7,16]. The analysis of the results was performed using FlowJo software (FlowJo 9.2, Tree Star, USA).…”

“…CD4 and CD8 Activation Markers. To determine activated CD4 and CD8, the same staining protocols previously described by our research group have been used [16].…”

“…Regarding CD8 T cells, the median value at T0 was 8% (6-18.1), at T1 month 8.2% (6.3-17.6), at T2 month 7.9% (5.9-17.4), at T3 month 8.1% (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), at T end 7.9% (6.5-19) and 7.9% (6.9-18), and at T post 7.9% (6.2-19).…”

“…The median value at T0 was 30.1% (8.8-31), at T1 month 29.5% (9-30), at T2 month 30% (8.3-29.8), at T3 month 30.2% (8-30), at T end 31.4%(8.7-32), and at T post 31.2%(8.5-31.5). Regarding CD8 T cells, the median value at T0 was 7% (4-22), at T1 month 7.5%(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23), at T2 month 7.1%(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22), at T3 month 7.3%(5.3-19), at T end 7.8% (4.5-2) and 13.9% (6.9-22), and at T post 7.3%(5-22.3).…”