Lymph node migratory dendritic cells modulate HIV-1 transcription through PD-1 engagement
| العنوان: | Lymph node migratory dendritic cells modulate HIV-1 transcription through PD-1 engagement |
|---|---|
| المؤلفون: | Riddhima Banga, Khalid Ohmiti, Matthieu Perreau, Kalliopi Ioannidou, Laurence de Leval, Francesco A. Procopio, Caterina Rebecchini, Alessandra Noto, Matthias Cavassini, Olivia Munoz, Giuseppe Pantaleo, Craig Fenwick, Jean-Marc Corpataux |
| المصدر: | PLoS pathogens, vol. 15, no. 7, pp. e1007918 PLoS Pathogens, Vol 15, Iss 7, p e1007918 (2019) PLoS Pathogens |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | RNA viruses, Transcription, Genetic, Physiology, Cell, Programmed Cell Death 1 Receptor, HIV Infections, Pathology and Laboratory Medicine, Memory T cells, White Blood Cells, Immunodeficiency Viruses, Transcription (biology), Cell Movement, Animal Cells, Medicine and Health Sciences, CD155, Receptors, Immunologic, Biology (General), Lymph node, 0303 health sciences, biology, Virulence, 030302 biochemistry & molecular biology, T-Lymphocytes, Helper-Inducer, Cell biology, Body Fluids, medicine.anatomical_structure, Blood, Cellular Microenvironment, Medical Microbiology, Viral Pathogens, Viruses, Anti-HIV Agents/therapeutic use, Antibodies, Monoclonal, Humanized/administration & dosage, Cell Movement/immunology, Cellular Microenvironment/immunology, Coculture Techniques, Dendritic Cells/immunology, Dendritic Cells/virology, Germinal Center/immunology, Germinal Center/virology, HIV Infections/drug therapy, HIV Infections/immunology, HIV Infections/virology, HIV-1/genetics, HIV-1/immunology, HIV-1/pathogenicity, Host Microbial Interactions/immunology, Humans, In Vitro Techniques, Lymph Nodes/immunology, Lymph Nodes/virology, Programmed Cell Death 1 Ligand 2 Protein/metabolism, Programmed Cell Death 1 Receptor/antagonists & inhibitors, Programmed Cell Death 1 Receptor/metabolism, Receptors, Immunologic/metabolism, Receptors, Virus/metabolism, T-Lymphocytes, Helper-Inducer/immunology, T-Lymphocytes, Helper-Inducer/virology, Receptors, Virus, Pathogens, Cellular Types, Anatomy, Research Article, Anti-HIV Agents, QH301-705.5, Immune Cells, Immunology, T cells, Antibodies, Monoclonal, Humanized, Microbiology, Lymphatic System, 03 medical and health sciences, TIGIT, Virology, Retroviruses, Genetics, medicine, T Helper Cells, Interleukin-7 receptor, Molecular Biology, Microbial Pathogens, 030304 developmental biology, Blood Cells, Host Microbial Interactions, Lentivirus, Organisms, Germinal center, Biology and Life Sciences, HIV, Dendritic Cells, Cell Biology, RC581-607, Germinal Center, Programmed Cell Death 1 Ligand 2 Protein, Immune checkpoint, Viral Replication, biology.protein, HIV-1, Parasitology, Lymph Nodes, Immunologic diseases. Allergy |
| الوصف: | T-follicular helper (Tfh) cells, co-expressing PD-1 and TIGIT, serve as a major cell reservoir for HIV-1 and are responsible for active and persistent HIV-1 transcription after prolonged antiretroviral therapy (ART). However, the precise mechanisms regulating HIV-1 transcription in lymph nodes (LNs) remain unclear. In the present study, we investigated the potential role of immune checkpoint (IC)/IC-Ligand (IC-L) interactions on HIV-1 transcription in LN-microenvironment. We show that PD-L1 (PD-1-ligand) and CD155 (TIGIT-ligand) are predominantly co-expressed on LN migratory (CD1chighCCR7+CD127+) dendritic cells (DCs), that locate predominantly in extra-follicular areas in ART treated individuals. We demonstrate that TCR-mediated HIV production is suppressed in vitro in the presence of recombinant PD-L1 or CD155 and, more importantly, when LN migratory DCs are co-cultured with PD-1+/Tfh cells. These results indicate that LN migratory DCs expressing IC-Ls may more efficiently restrict HIV-1 transcription in the extra-follicular areas and explain the persistence of HIV transcription in PD-1+/Tfh cells after prolonged ART within germinal centers. Author summary Increasing number of evidences indicate that B-cell follicles might be anatomical sanctuaries for active transcription in both HIV/SIV viremic controllers and in ART treated aviremic HIV-infected individuals. While multiple mechanisms may be involved in the regulation of HIV transcription, recent studies suggested that immune checkpoint molecule (IC) signaling may contribute to maintain HIV-1 latency in infected CD4 T cells. These observations prompted us to investigate the involvement of IC/IC-L interactions in the regulation of HIV-1 transcription in lymph node (LN) tissues. In the present study, we show that T follicular helper (Tfh) cells predominantly co-expressed PD-1 and TIGIT, which were functionally active. An in-depth mass cytometry analysis revealed that PD-L1, PD-L2 (PD-1 ligands) and CD155 (TIGIT-ligand) were predominantly co-expressed on a specific LN dendritic cell (DC) subpopulation expressing markers of migratory DCs. We subsequently demonstrated that LN migratory DCs, locating predominantly in LN extra-follicular areas, could modulate HIV-1 transcription by a mechanism involving PD-L1/PD-1 interactions. Interestingly, the frequency of LN migratory DCs inversely correlated with HIV-1 transcription from LN memory CD4 T cells, suggesting that IC-L expressing migratory DCs might contribute to control HIV-1 transcription and maintain HIV-1 latency in extra-follicular areas. These findings represent a step forward in our understanding of potential mechanisms contributing to the regulation of HIV persistence in lymphoid tissues. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6a75d9b74797de056653603fd5facae8 https://serval.unil.ch/resource/serval:BIB_1FF4BBBC8958.P001/REF.pdf |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....6a75d9b74797de056653603fd5facae8 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |