Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs
| العنوان: | Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs |
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| المؤلفون: | Cécile Goujard, Benoit Favier, Sixtine Coindre, Nathalie Dereuddre-Bosquet, Gustavo Palomino, Lamine Alaoui, Roger Le Grand, Pierre Roques, Christine Bourgeois, S Zurawski, Olivier Lambotte, Camille Lécuroux, Bruno Vaslin, Gerard Zurawski |
| المصدر: | Cellular and Molecular Life Sciences. 75:1871-1887 |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Time Factors, Population, Simian Acquired Immunodeficiency Syndrome, HIV Infections, medicine.disease_cause, Major histocompatibility complex, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Immune system, MHC class I, medicine, Animals, Humans, Receptors, Immunologic, education, Molecular Biology, Cells, Cultured, Pharmacology, education.field_of_study, Membrane Glycoproteins, Innate immune system, biology, Histocompatibility Antigens Class I, virus diseases, Dendritic Cells, Cell Biology, TLR7, Middle Aged, Immune dysregulation, Virology, Immune checkpoint, Macaca fascicularis, 030104 developmental biology, HIV-1, biology.protein, Molecular Medicine, Female, Simian Immunodeficiency Virus, 030215 immunology |
| الوصف: | Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response. |
| تدمد: | 1420-9071 1420-682X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b92d53b4973d8f86eb3f09bf421cbcf1Test https://doi.org/10.1007/s00018-017-2712-9Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....b92d53b4973d8f86eb3f09bf421cbcf1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14209071 1420682X |
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