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• W1548106543 endingPage "1948" @default.
• W1548106543 startingPage "1939" @default.
• W1548106543 abstract "Dendritic cells (DCs) are likely to play a key role in immunity against Mycobacterium tuberculosis, but the fate of the bacterium in these cells is still unknown. Here we report that, unlike macrophages (Mphis), human monocyte-derived DCs are not permissive for the growth of virulent M. tuberculosis H37Rv. Mycobacterial vacuoles are neither acidic nor fused with host cell lysosomes in DCs, in a mode similar to that seen in mycobacterial infection of Mphis. However, uptake of the fluid phase marker dextran, and of transferrin, as well as accumulation of the recycling endosome-specific small GTPase Rab11 onto the mycobacterial phagosome, are almost abolished in infected DCs, but not in Mphis. Moreover, communication between mycobacterial phagosomes and the host-cell biosynthetic pathway is impaired, given that <10% of M. tuberculosis vacuoles in DCs stained for the endoplasmic reticulum-specific proteins Grp78/BiP and calnexin. This correlates with the absence of the fusion factor N-ethylmaleimide-sensitive factor onto the vacuolar membrane in this cell type. Trafficking between the vacuoles and the host cell recycling and biosynthetic pathways is strikingly reduced in DCs, which is likely to impair access of intracellular mycobacteria to essential nutrients and may thus explain the absence of mycobacterial growth in this cell type. This unique location of M. tuberculosis in DCs is compatible with their T lymphocyte-stimulating functions, because M. tuberculosis-infected DCs have the ability to specifically induce cytokine production by autologous T lymphocytes from presensitized individuals. DCs have evolved unique subcellular trafficking mechanisms to achieve their Ag-presenting functions when infected by intracellular mycobacteria." @default.
• W1548106543 created "2016-06-24" @default.
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• W1548106543 date "2003-02-15" @default.
• W1548106543 modified "2023-10-18" @default.
• W1548106543 title "Constrained Intracellular Survival of <i>Mycobacterium tuberculosis</i> in Human Dendritic Cells" @default.
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• W1548106543 doi "https://doi.org/10.4049/jimmunol.170.4.1939" @default.
• W1548106543 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12574362" @default.
• W1548106543 hasPublicationYear "2003" @default.
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