التفاصيل البيبلوغرافية
| العنوان: |
Spatiotemporal trafficking of HIV in human plasmacytoid dendritic cells defines a persistently IFN-α-producing and partially matured phenotype. |
| المؤلفون: |
O'Brien, Meagan1,2, Manches, Olivier2, Sabado, Rachel Lubong2, Baranda, Sonia Jimenez2, Wang, Yaming3, Marie, Isabelle3, Rolnitzky, Linda4, Markowitz, Martin5, Margolis, David M.6, Levy, David3, Bhardwaj, Nina2,3 |
| المصدر: |
Journal of Clinical Investigation. Mar2011, Vol. 121 Issue 3, p1088-1101. 14p. 1 Color Photograph, 3 Charts, 8 Graphs. |
| مصطلحات موضوعية: |
*HIV, *DENDRITIC cells, *PHENOTYPES, *IMMUNE response, *T cells, *PROTEIN metabolism, *RNA metabolism, *CARRIER proteins, *CELL receptors, *COMPARATIVE studies, *CYTOKINES, *HIV infections, *IMMUNE system, *RESEARCH methodology, *MEDICAL cooperation, *RESEARCH, *TIME, *DNA-binding proteins, *EVALUATION research |
| مستخلص: |
Plasmacytoid DCs (pDCs) are innate immune cells that are specialized to produce IFN-α and to activate adaptive immune responses. Although IFN-α inhibits HIV-1 replication in vitro, the production of IFN-α by HIV-activated pDCs in vivo may contribute more to HIV pathogenesis than to protection. We have now shown that HIV-stimulated human pDCs allow for persistent IFN-α production upon repeated stimulation, express low levels of maturation molecules, and stimulate weak T cell responses. Persistent IFN-α production by HIV-stimulated pDCs correlated with increased levels of IRF7 and was dependent upon the autocrine IFN-α/β receptor feedback loop. Because it has been shown that early endosomal trafficking of TLR9 agonists causes strong activation of the IFN-α pathway but weak activation of the NF-κB pathway, we sought to investigate whether early endosomal trafficking of HIV, a TLR7 agonist, leads to the IFN-α-producing phenotype we observed. We demonstrated that HIV preferentially traffics to the early endosome in human pDCs and therefore skews pDCs toward a partially matured, persistently IFN-α-secreting phenotype. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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