Dendritic cells at the interface of innate and adaptive immunity to HIV-1

Department of Microbiology, Tumor and Cell Biology bCenter for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
Current opinion in HIV and AIDS (Impact Factor: 4.68). 09/2011; 6(5):405-10. DOI: 10.1097/COH.0b013e328349b06b
Source: PubMed


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.

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    • "HIV-1 impairs the functions of CD4+ T cells, CD8+T cells, B cells and natural killer cells [15]. However, how HIV-1 Nef influences dendritic cells (DCs) responsible for initiating and modulating immunity remains unclear [16], [17], [18], [19], [20]. Our recent studies have indicated that intracellular over-expression of Rev, Tat, Vif, Vpr and Vpu could induce apoptosis of THP-1 except for Nef. "
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    ABSTRACT: Nef functions as an immunosuppressive factor critical for HIV-1 replication, survival and development of AIDS following HIV-1 infection. What effects Nef exerts on differentiation and maturation of monocytes towards dendritic cells (DCs) remains greatly controversial. In this study, we used THP-1 (human monocytic leukemia cell line) as monocytic DC precursors to investigate how overexpression of HIV-1 Nef influences the processes of differentiation and maturation of dendritic cells. In striking contrast to negative controls, our results showed that morphological and phenotypical changes (CD11c, CD14, CD40, CD80, CD83, CD86, and HLA-DR) occurred on recombinant THP-1 expressing HIV-1 Nef (short for Nef) upon co-stimulation of GM-CSF/IL-4 or GM-CSF/IL-4/TNF-α/ionomycin. Moreover, CD4, CCR5, and CXCR4 were also down-regulated on Nef. It might be hypothesized that Nef prevents superinfection and signal transduction in HIV-1 infected monocytes. Collectively, our study demonstrates that long-lasting expression of Nef at high levels indeed retards differentiation and maturation of dendritic cells in terms of phenotype and morphology. We are hopeful that potentially, stable expression of intracellular Nef in vivo may function as a subtle mode to support long-lasting HIV-1 existence.
    Preview · Article · Jul 2012 · PLoS ONE
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    • "Recent data indicate that pDCs infected in vitro with HIV may be modified by the virus to reach a semi-mature stage that facilitates Treg induction (Smed-Sorensen and Lore, 2011). Similar observations have been made with tumor-infiltrating pDCs that show impaired maturation potential but without providing T cell assays (Perrot et al., 2007; Tjomsland et al., 2010). "
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    ABSTRACT: Dendritic cells (DCs) are major players in the control of adaptive tolerance and immunity. Therefore, their specific generation and adoptive transfer into patients or their in vivo targeting is attractive for clinical applications. While injections of mature immunogenic DCs are tested in clinical trials, tolerogenic DCs still are awaiting this step. Besides the tolerogenic potential of immature DCs, also semi-mature DCs can show tolerogenic activity but both types also bear unfavorable features. Optimal tolerogenic DCs, their molecular tool bar, and their use for specific diseases still have to be defined. Here, the usefulness of in vitro generated and adoptively transferred semi-mature DCs for tolerance induction is outlined. The in vivo targeting of semi-mature DCs as represented by steady state migratory DCs are discussed for treatment of autoimmune diseases and allergies. First clinical trials with transcutaneous allergen application may point to their therapeutic use in the future.
    Preview · Article · May 2012 · Frontiers in Immunology
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    • "In contrast, the capacity to maintain immune homeostasis at mucosal sites will probably allow for better control of HIV-infection. The general effects of HIV-infection and disease on DC populations have been recently reviewed [1] [2] [3] [4] and are beyond the scope of this work. This perspective review will focus on the potential impact of DCs on HIV-related B-cell disorders and responses. "
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    ABSTRACT: Dendritic cells (DCs) modulate B-cell differentiation, activation, and survival mainly through production of growth factors such as B lymphocyte stimulator (BLyS/BAFF). DC populations have been reported to be affected in number, phenotype and function during HIV infection and such alterations may contribute to the dysregulation of the B-cell compartment. Herein, we reflect on the potential impact of DC on the pathogenesis of HIV-related B cell disorders, and how DC status may modulate the outcome of mucosal B cell responses against HIV, which are pivotal to the control of disease. A concept that could be extrapolated to the overall outcome of HIV disease, whereby control versus progression may reside in the host's capacity to maintain DC homeostasis at mucosal sites, where DC populations present an inherent capacity of modulating the balance between tolerance and protection, and are amongst the earliest cell types to be exposed to the virus.
    Full-text · Article · Feb 2012 · Clinical and Developmental Immunology
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