Dendritic Cells in Innate Immune Responses Against HIV

Servet, Christine; Zitvogel, Laurence; Hosmalin, Anne

doi:10.2174/1566524023361907

Cited by 46 publications

(30 citation statements)

References 140 publications

(205 reference statements)

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“…Our findings indicate that mDC and pDC undergo spontaneous cell death during culture, supporting the hypothesis that the loss of DC may be due to cell death (39,40). Notably, the amine reactive viability dye used in this study identifies not only necrotic but also late or postapoptotic cells (41), and preliminary experiments have identified viable DC in the lymph nodes of monkeys with AIDS that are annexin Vpositive (data not shown), suggesting that the DC may be undergoing apoptosis.…”

Section: Discussionsupporting

confidence: 83%

Parallel Loss of Myeloid and Plasmacytoid Dendritic Cells from Blood and Lymphoid Tissue in Simian AIDS

Brown

Trichel²,

Barratt‐Boyes

2007

The Journal of Immunology

105

141

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The loss of myeloid (mDC) and plasmacytoid dendritic cells (pDC) from the blood of HIV-infected individuals is associated with progressive disease. It has been proposed that DC loss is due to increased recruitment to lymph nodes, although this has not been directly tested. Similarly as in HIV-infected humans, we found that lineage-negative (Lin−) HLA-DR+CD11c+CD123− mDC and Lin−HLA-DR+CD11c−CD123+ pDC were lost from the blood of SIV-infected rhesus macaques with AIDS. In the peripheral lymph nodes of SIV-naive monkeys the majority of mDC were mature cells derived from skin that expressed high levels of HLA-DR, CD83, costimulatory molecules, and the Langerhans cell marker CD1a, whereas pDC expressed low levels of HLA-DR and CD40 and lacked costimulatory molecules, similar to pDC in blood. Surprisingly, both DC subsets were depleted from peripheral and mesenteric lymph nodes and spleens in monkeys with AIDS, although the activation status of the remaining DC subsets was similar to that of DC in health. In peripheral and mesenteric lymph nodes from animals with AIDS there was an accumulation of Lin−HLA-DRmoderateCD11c−CD123− cells that resembled monocytoid cells but failed to acquire a DC phenotype upon culture, suggesting they were not DC precursors. mDC and pDC from the lymphoid tissues of monkeys with AIDS were prone to spontaneous death in culture, indicating that apoptosis may be a mechanism for their loss in disease. These findings demonstrate that DC are lost from rather than recruited to lymphoid tissue in advanced SIV infection, suggesting that systemic DC depletion plays a direct role in the pathophysiology of AIDS.

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Section: Discussionsupporting

confidence: 83%

Parallel Loss of Myeloid and Plasmacytoid Dendritic Cells from Blood and Lymphoid Tissue in Simian AIDS

Brown

Trichel²,

Barratt‐Boyes

2007

The Journal of Immunology

105

141

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“…We found that HIV-1 induced TRAIL and IFN-␣ production by monocytes, which may contribute to the high levels of both cytokines in patients (10), despite the reported reduction of blood pDCs in progressive HIV-1 disease (17,30). This reduction of circulating pDCs may be due to their redistribution to lymphoid tissue (31), which could result in IFN production, leading to TRAIL expression by CD4 ϩ T cells and apoptosis of DR5 ϩ CD4 ϩ T cells (11). This hypothesis is consistent with our finding that HIV-1 induced TRAIL production in ex vivo tonsil cultures (10).…”

Section: Discussionmentioning

confidence: 66%

Regulation of TNF-related apoptosis-inducing ligand on primary CD4 ⁺ T cells by HIV-1: Role of type I IFN-producing plasmacytoid dendritic cells

Herbeuval

Hardy

Boasso

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

147

143

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TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, was suggested to contribute to HIV-1 pathogenesis by inducing CD4 ؉ T cell death characteristic of AIDS. We previously reported HIV-1-mediated, TRAIL-induced apoptosis in primary CD4 ؉ T cells in vitro and observed elevated levels of plasma TRAIL in HIV-1-infected patients. The present study elucidates the unresolved mechanism by which HIV-1 induces TRAIL expression on primary CD4 ؉ T cells. We demonstrate that the expression of TRAIL by primary CD4 ؉ T cells is regulated by IFN-␣ that is produced by HIV-1-stimulated plasmacytoid dendritic cells (pDCs). We also found that IFN-induced TRAIL is mediated by signal transducers and activators of transcription 1 and 2. We show that IFN-␣ production by HIV-1-activated pDCs is blocked by an early viral entry inhibitor of CD4-gp120 binding, but not by inhibitors of viral coreceptor binding. Our in vitro data are supported by the demonstration that anti-IFN-␣ and -␤ Abs inhibit apoptosis and TRAIL expression in CD4 ؉ T cells from HIV-1-infected patients. Our findings suggest a potential unique role of pDCs in the immunopathogenesis of HIV-1 infection by inducing the death molecule TRAIL.T NF-related apoptosis-inducing ligand (TRAIL), a TNF superfamily member (1), has two death receptors (DRs) that induce apoptosis (2) (DR4 and DR5) and three other receptors that lack the death domain and engage ligand without initiating apoptosis (3). TRAIL protein is expressed on the cell membrane (mTRAIL) or is secreted (soluble TRAIL) (1), and both the soluble and membrane-bound forms induce apoptosis of cells expressing functional DRs (4). TRAIL may contribute to HIV-1 immunopathogenesis because CD4 ϩ and CD8 ϩ T cells from HIV-1-infected patients are more susceptible to TRAILinduced apoptosis in vitro than T cells from healthy donors (5-7). TRAIL induced the selective apoptosis of uninfected CD4 ϩ T cells in HIV-1-infected hu-PBL-NOD-SCID mice (8). TRAIL, produced by monocytes exposed to the HIV-1 Tat protein, induced apoptosis of uninfected CD4 ϩ T cells (9). We recently reported that plasma TRAIL levels in HIV-1-infected patients directly correlate with viral load (10). We also reported that CD4 ϩ T cells exposed to HIV-1 underwent apoptosis by a TRAIL-DR5-dependent mechanism, which was inhibited by anti-type I IFN Abs (11). These latter results suggest that type I IFN plays a fundamental role in HIV-1-induced TRAIL expression by CD4 ϩ T cells.Type I IFN (IFN-␣͞␤) has antiviral activity, including activity against HIV-1 (12). IFN-␣͞␤ are produced mainly by plasmacytoid dendritic cells (pDCs) (13). pDCs are located in blood and lymphoid tissue (13-15) and participate in innate immune responses against viruses by producing large amounts of 17). Interestingly, pDCs secrete type I IFN when stimulated by infectious HIV-1 or chemically inactivated HIV-1 virions (18). The majority of plasma HIV-1 is not infectious (19,20), raising the possibility that such virions contribute to HIV-1 pathogenesis and CD4 ϩ T c...

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“…DCs may play a central role in MV-associated immunosuppression. One suggested mechanism is TRAIL-mediated apoptosis of T cells (42). However, TRAIL was similarly induced by all pathogens and therefore is not a unique mechanism for immunosuppression in measles.…”

Section: Discussionmentioning

confidence: 99%

Gene expression patterns in dendritic cells infected with measles virus compared with other pathogens

Zilliox

Parmigiani

Griffin

2006

Proc. Natl. Acad. Sci. U.S.A.

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Gene expression patterns supply insight into complex biological networks that provide the organization in which viruses and host cells interact. Measles virus (MV) is an important human pathogen that induces transient immunosuppression followed by life-long immunity in infected individuals. Dendritic cells (DCs) are potent antigen-presenting cells that initiate the immune response to pathogens and are postulated to play a role in MV-induced immunosuppression. To better understand the interaction of MV with DCs, we examined the gene expression changes that occur over the first 24 h after infection and compared these changes to those induced by other viral, bacterial, and fungal pathogens. There were 1,553 significantly regulated genes with nearly 60% of them down-regulated. MV-infected DCs up-regulated a core of genes associated with maturation of antigen-presenting function and migration to lymph nodes but also included genes for IFN-regulatory factors 1 and 7, 2 5 oligoadenylate synthetase, Mx, and TNF superfamily proteins 2, 7, 9, and 10 (TNF-related apoptosisinducing ligand). MV induced genes for IFNs, ILs, chemokines, antiviral proteins, histones, and metallothioneins, many of which were also induced by influenza virus, whereas genes for protein synthesis and oxidative phosphorylation were down-regulated. Unique to MV were the induction of genes for a broad array of IFN-␣s and the failure to up-regulate dsRNA-dependent protein kinase. These results provide a modular view of common and unique DC responses after infection and suggest mechanisms by which MV may modulate the immune response.immunosuppression ͉ IFN ͉ microarray ͉ dsRNA-dependent protein kinase

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Dendritic Cells in Innate Immune Responses Against HIV

Cited by 46 publications

References 140 publications

Parallel Loss of Myeloid and Plasmacytoid Dendritic Cells from Blood and Lymphoid Tissue in Simian AIDS

Parallel Loss of Myeloid and Plasmacytoid Dendritic Cells from Blood and Lymphoid Tissue in Simian AIDS

Regulation of TNF-related apoptosis-inducing ligand on primary CD4 ⁺ T cells by HIV-1: Role of type I IFN-producing plasmacytoid dendritic cells

Gene expression patterns in dendritic cells infected with measles virus compared with other pathogens

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Dendritic Cells in Innate Immune Responses Against HIV

Cited by 46 publications

References 140 publications

Parallel Loss of Myeloid and Plasmacytoid Dendritic Cells from Blood and Lymphoid Tissue in Simian AIDS

Parallel Loss of Myeloid and Plasmacytoid Dendritic Cells from Blood and Lymphoid Tissue in Simian AIDS

Regulation of TNF-related apoptosis-inducing ligand on primary CD4 + T cells by HIV-1: Role of type I IFN-producing plasmacytoid dendritic cells

Gene expression patterns in dendritic cells infected with measles virus compared with other pathogens

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Regulation of TNF-related apoptosis-inducing ligand on primary CD4 ⁺ T cells by HIV-1: Role of type I IFN-producing plasmacytoid dendritic cells