Dendritic cells at the interface of innate and adaptive immunity to HIV-1.
ABSTRACT This review summarizes recent findings on how HIV-1 infection affects dendritic cells in their ability to elicit innate and adaptive immune responses.
The phenomenon describing a reduction of dendritic cell numbers in the blood of HIV-1-infected individuals has been expanded on in recent studies demonstrating that dendritic cells decline very early in primary infection and that there is a mobilization of semi-mature dendritic cells to lymph nodes. Recent data suggest that dendritic cells in lymph nodes are more prone to apoptosis, which correlates with disease progression. In addition, plasmacytoid dendritic cells isolated from blood showed a semi-mature phenotype after HIV-1 exposure, which coincided with persistent IFN-α secretion. Emerging data show that semi-mature dendritic cells induce regulatory T cells and suppress effector function. There may therefore be mechanisms by which HIV-1 affects dendritic cell immune stimulation and, in doing so, interferes with the elicitation of anti-HIV-1 responses.
Understanding how dendritic cells are functionally altered during HIV-1 infection is crucial for the development of new immune-therapy strategies including approaches to target dendritic cells with antigen in vivo or ex vivo to induce efficient adaptive anti-HIV immunity.
SourceAvailable from: Rogerio Gondak[Show abstract] [Hide abstract]
ABSTRACT: The purpose of this study was to quantify and compare the density of dendritic cells (DCs) in cervical lymph nodes (LNs) and palatine tonsils (PTs) of AIDS and non-AIDS patients. Factor XIIIa, CD1a and CD83 antibodies were used to identify migratory DCs by immunohistochemistry in LNs and PTs of 32 AIDS patients and 21 HIV-negative control patients. Quantification was performed by the positive pixel count analytical method. AIDS patients presented a lower density of factor XIIIa(+) cells (P < 0.001), CD1a(+) cells (P < 0.05) and CD83(+) cells (P < 0.001) in cervical LNs and PTs compared to the non-AIDS control group. Overall depletion of DCs in lymphoid tissues of AIDS patients may be predictive of the immune system's loss of disease control.Histopathology 08/2013; 64(2). DOI:10.1111/his.12256 · 3.30 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Dendritic cells (DCs) modulate B-cell survival and differentiation, mainly through production of growth factors such as B lymphocyte stimulator (BLyS/BAFF). We have recently shown that in HIV-1-infected rapid and classic progressors B-cell dysregulations were associated with increased BLyS/BAFF expression in plasma and by blood myeloid DCs (mDCs), in contrast to aviremic slow progressors, also known as elite controllers. In previous work with HIV-transgenic mice, B-cell dysregulations were concomitant with altered mDCs and dependant on HIV negative factor (Nef). We now report that HIV-1-Nef is detected in plasma and BLyS/BAFF over-expressing blood mDCs of HIV-1-infected rapid and classic progressors, early on infection and despite successful therapy, whereas it is low to undetectable in aviremic slow progressors. In vitro, HIV-1-Nef drives monocyte-derived DCs towards BLyS/BAFF over-expression, through a process involving STAT1. Importantly, this is counteracted in presence of all-trans retinoic acid. Nef thus contributes to high BLyS/BAFF pro-inflammatory profiles in HIV-1-infected individuals.
[Show abstract] [Hide abstract]
ABSTRACT: In mice, CD8α(+) myeloid dendritic cells (mDC) optimally cross-present Ags to CD8(+) T cells and respond strongly to TLR3 ligands. Although equivalent DC have been identified by comparative genomic analysis and functional studies in humans as XCR1(+)CD141 (BDCA-3)(+)Clec9A(+)cell adhesion molecule 1(+) mDC, and in sheep as CD26(+) mDC, these cells remained elusive in nonhuman primates. To remedy this situation, we delineated precisely DC and monocyte populations by 12-color flow cytometry and transcriptomic analyses in healthy rhesus macaques. We identified a new mDC population, with strong phenotypic and transcriptional homology to human CD141(+) and murine CD8α(+) mDC, including XCR1 membrane expression as a conserved specific marker. In contrast, high CD11c expression was not characteristic of mDC in macaques, but of CD16(+) monocytes. Like their human and murine homologs, simian XCR1(+) mDC had much stronger responses to TLR3 stimulation than other myeloid cells. The importance of this new mDC population was tested in SIVmac251 infection, the most relevant animal model for pathogenic HIV-1 infection and vaccination. This population increased sharply and transiently during acute infection, but was reduced in blood and spleen during advanced disease. The identification of XCR1(+) mDC in rhesus macaques opens new avenues for future preclinical vaccinal studies and highlights XCR1 as a prime candidate for targeted vaccine delivery.The Journal of Immunology 04/2014; 192(10). DOI:10.4049/jimmunol.1302448 · 5.36 Impact Factor