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.
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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.Clinical and Developmental Immunology 02/2012; 2012:592187. DOI:10.1155/2012/592187 · 2.93 Impact Factor
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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.Frontiers in Immunology 05/2012; 3:123. DOI:10.3389/fimmu.2012.00123
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ABSTRACT: It has been emphasized that chronic generalized immune dysfunction is the leading event in the pathogenesis of HIV infection, in which the contribution of dendritic cells (DCs) and regulatory T cells (Tregs) should not be underestimated. In current study, we assessed the longitudinal changes of peripheral blood DC subsets and Tregs in chronically asymptomatic treatment-naive HIV-1-infected patients during 60 weeks of antiretroviral therapy (ART), and compared with those in healthy controls and long term non-progressors (LTNPs). Blood samples were collected at week 0, 4, 12, 24, 48 and 60 of treatment to measure the counts of DC subsets and Tregs by flow cytometry and IFN-a plasma levels by ELISA. The counts of myeloid dendritic cells (mDCs) increased during ART, reaching similar levels to healthy controls at week 60 post ART but still lower than those of LTNPs. In HIV-1-infected patients, the mDCs counts were directly correlated with CD4 counts during ART. Changes in mDCs at week 8 were positively correlated with the changes in CD4 counts at week 60 post ART. However, the counts and function of plasmacytoid dendritic cells (pDCs) remained relatively stable during ART, and similar to those in healthy controls and LTNPs. The percentage of Tregs increased before ART and normalized after ART. Importantly, we found pDCs counts were associated with percentage of Tregs during ART, which may help in understanding of the role of these cells in HIV infection.PLoS ONE 05/2012; 7(5):e37966. DOI:10.1371/journal.pone.0037966 · 3.53 Impact Factor