20 research outputs found

    Major Depletion of Plasmacytoid Dendritic Cells in HIV-2 Infection, an Attenuated Form of HIV Disease

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    Plasmacytoid dendritic cells (pDC) provide an important link between innate and acquired immunity, mediating their action mainly through IFN-α production. pDC suppress HIV-1 replication, but there is increasing evidence suggesting they may also contribute to the increased levels of cell apoptosis and pan-immune activation associated with disease progression. Although having the same clinical spectrum, HIV-2 infection is characterized by a strikingly lower viremia and a much slower rate of CD4 decline and AIDS progression than HIV-1, irrespective of disease stage. We report here a similar marked reduction in circulating pDC levels in untreated HIV-1 and HIV-2 infections in association with CD4 depletion and T cell activation, in spite of the undetectable viremia found in the majority of HIV-2 patients. Moreover, the same overexpression of CD86 and PD-L1 on circulating pDC was found in both infections irrespective of disease stage or viremia status. Our observation that pDC depletion occurs in HIV-2 infected patients with undetectable viremia indicates that mechanisms other than direct viral infection determine the pDC depletion during persistent infections. However, viremia was associated with an impairment of IFN-α production on a per pDC basis upon TLR9 stimulation. These data support the possibility that diminished function in vitro may relate to prior activation by HIV virions in vivo, in agreement with our finding of higher expression levels of the IFN-α inducible gene, MxA, in HIV-1 than in HIV-2 individuals. Importantly, serum IFN-α levels were not elevated in HIV-2 infected individuals. In conclusion, our data in this unique natural model of “attenuated” HIV immunodeficiency contribute to the understanding of pDC biology in HIV/AIDS pathogenesis, showing that in the absence of detectable viremia a major depletion of circulating pDC in association with a relatively preserved IFN-α production does occur

    Shapes, Paint, and Light

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    A fundamental problem in computer vision is that of inferring the intrinsic, 3D structure of the world from flat, 2D images of that world. Traditional methods for recovering scene properties such as shape, reflectance, or illumination rely on multiple observations of the same scene to overconstrain the problem. Recovering these same properties from a single image seems almost impossible in comparison — there are an infinite number of shapes, paint, and lights that exactly reproduce a single image. However, certain explanations are more likely than others: surfaces tend to be smooth, paint tends to be uniform, and illumination tends to be natural. We therefore pose this problem as one of statistical inference, and define an optimization problem that searches for the most likely explanation of a single image. Our model, which we call “SIRFS”, can be viewed as a superset of several classic computer vision problems (shape-from-shading, intrinsic images, color constancy, illumination estimation, etc) and outperforms all previous solutions to those constituent problems. Though SIRFS performs well on images of segmented objects, it performs poorly on images of natural scenes, which contain occlusion and spatially-varying illumination. We therefore additionally present Scene-SIRFS, a generalization of SIRFS in which we have a mixture of shapes and a mixture of illuminations, and those mixture components are embedded in a “soft ” segmentation of the input image. We additionally use the noisy depth maps provided by RGB-D sensors (in this case, the Kinect) to improve shape estimation. iTo Estee, Shelley, Laura, and Will. i
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