Article

Influence of Plasma Viremia on Defects in Number and Immunophenotype of Blood Dendritic Cell Subsets in Human Immunodeficiency Virus 1–Infected Individuals

Department of Medicine, University of Colorado, Denver, Colorado, United States
The Journal of Infectious Diseases (Impact Factor: 5.78). 02/2003; 187(1):26-37. DOI: 10.1086/345957
Source: PubMed

ABSTRACT Dendritic cells (DCs) are postulated to be involved in transmission of human immunodeficiency virus (HIV) type 1 to T cells and in stimulation of HIV-1-specific cell-mediated immunity. Blood DCs have been categorized as myeloid (mDC) and plasmacytoid (pDC) subsets, on the basis of differences in phenotype and function. Blood DC subset numbers and expression of costimulatory molecules and HIV-1 coreceptors on DCs were measured in the blood of treated and untreated HIV-1-infected subjects and uninfected control subjects. Absolute numbers of mDCs and pDCs were lower in HIV-1-infected subjects than in control subjects, most significantly in those with active HIV-1 replication. Increased surface expression of costimulatory molecules was observed on both DC subsets in subjects with HIV-1 viremia. Highly active antiretroviral therapy suppression of plasma viremia resulted in increases in blood DC numbers and decreases in DC costimulatory molecule expression. These findings further define the impact of HIV-1 replication on blood DC subsets in vivo.

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    • "In HIV infection it has been demonstrated a reduction in absolute number of mDC and pDC, especially in patients with active HIV-1 replication [3], suggesting a key role of DC in controlling viral load. Moreover the preserved functionality of pDC isolated from “elite controllers” may be one of the mechanisms involved in the control of HIV-1 viremia in these subjects [4]. "
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    ABSTRACT: NLRP3-inflammasome activation was evaluated in monocyte-derived dendritic cells (DC) obtained through IL-4 (IL4-DC) or IFN-alpha (IFN-DC) protocols and pulsed with chemically inactivated HIV-1. Inflammasome' genes expression and IL-1ss secretion were compared in DC isolated from 15 healthy subjects (HC) and 10 HIV-1 infected individuals (HIV+). Whether HIV was able to increased NLRP3-inflammasome genes expression and IL-1ss secretion in IL4-DC from HC, the induction of inflammasome appeared significantly reduced in IFN-DC from HC, suggesting a different responsive state of IFN-DC compared to IL4-DC. No inflammasome activation was observed in IL4-DC as well as in IFN-DC derived from HIV + subjects, confirming previous findings on "unresponsive" state of DC derived from HIV + possibly due to chronic inflammatory state of these individuals. Our results showed that IFN-alpha differently modulates inflammasome expression during monocytes-DC in vitro differentiation. These findings could be of interest considering the on-going research about DC manipulation and therapeutic strategies for HIV + involving DC-based immune-vaccines.
    AIDS Research and Therapy 12/2013; 10(1):35. DOI:10.1186/1742-6405-10-35 · 1.84 Impact Factor
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    • "This includes low CD4 T cell counts, CD4 T cell expression of markers associated with activation and exhaustion [14], [30], as well as CD8 T cell activation [9], [10], [11], [12], [13], [14]. Likewise, the patterns of decreased levels of mDCs [31], [32], [33], Treg cells [34], [35] and iNKT cells [36], [37], [38], increased PD-1 expression on iNKT cells [39], as well as increased plasma levels of sCD14 [14], [40], in CVID patients are shared with HIV-1 infected patients. Interestingly, it was previously reported that CVID patients with lower naïve CD4 T cell levels display worse clinical scores [41], and, in line with the present data, that CVID patients display a pattern of L-selectin and CD38 expression on CD8 T cells similar to that observed in HIV-1 infected patients [42]. "
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    PLoS ONE 10/2013; 8(10):e75199. DOI:10.1371/journal.pone.0075199 · 3.23 Impact Factor
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    • "Untreated chronic HIV-1-infected patients under HAART recovered mDC numbers in contrast to a sustained loss of pDCs in parallel with decreased IFN-α secretion [42], [43]. The decline of pDCs inversely correlates with viral load and is associated with a decrease in the level of IFN-α production per cell and lower CD4+ T cell counts [44], [45]. Evidence of immune exhaustion in pDCs and a better reconstitution of pDCs in patients treated with HAART early argue that an earlier start to therapy results in preservation of pDC numbers and function [46]. "
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    PLoS ONE 06/2013; 8(6):e67036. DOI:10.1371/journal.pone.0067036 · 3.23 Impact Factor
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