دورية أكاديمية
Spatiotemporal trafficking of HIV in human plasmacytoid dendritic cells defines a persistently IFN-α–producing and partially matured phenotype
| العنوان: | Spatiotemporal trafficking of HIV in human plasmacytoid dendritic cells defines a persistently IFN-α–producing and partially matured phenotype |
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| المؤلفون: | O’Brien, Meagan, Manches, Olivier, Sabado, Rachel Lubong, Jimenez Baranda, Sonia, Wang, Yaming, Marie, Isabelle, Rolnitzky, Linda, Markowitz, Martin, Margolis, David M., Levy, David, Bhardwaj, Nina |
| المصدر: | Journal of Clinical Investigation, 121(3) |
| سنة النشر: | 2011 |
| المجموعة: | Carolina Digital Repository (UNC - University of North Carolina) |
| مصطلحات موضوعية: | Phenotype, Time Factors, HIV Infections, Immune System, Humans, RNA, Messenger, Toll-Like Receptor 9, Suppressor of Cytokine Signaling Proteins, Suppressor of Cytokine Signaling 3 Protein, HIV, Cytokines, NF-kappa B, Dendritic Cells, Suppressor of Cytokine Signaling 1 Protein, Interferon-alpha |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.17615/r5qp-d365Test; https://cdr.lib.unc.edu/downloads/f7623m21t?file=thumbnailTest; https://cdr.lib.unc.edu/downloads/f7623m21tTest |
| DOI: | 10.17615/r5qp-d365 |
| الإتاحة: | https://doi.org/10.17615/r5qp-d365Test https://cdr.lib.unc.edu/downloads/f7623m21t?file=thumbnailTest https://cdr.lib.unc.edu/downloads/f7623m21tTest |
| حقوق: | http://rightsstatements.org/vocab/InC/1.0Test/ |
| رقم الانضمام: | edsbas.F74FDAA3 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17615/r5qp-d365 |
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