IL-17A reprograms intestinal epithelial cells to facilitate HIV-1 replication and outgrowth in CD4+ T cells
Summary: The crosstalk between intestinal epithelial cells (IECs) and Th17-polarized CD4+ T cells is critical for mucosal homeostasis, with HIV-1 causing significant alterations in people living with HIV (PLWH) despite antiretroviral therapy (ART). In a model of IEC and T cell co-cultures, we invest...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-11-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221011937 |
| _version_ | 1819000929579433984 |
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| author | Tomas Raul Wiche Salinas Annie Gosselin Laurence Raymond Marchand Etiene Moreira Gabriel Olivier Tastet Jean-Philippe Goulet Yuwei Zhang Dragos Vlad Hanane Touil Jean-Pierre Routy Mariana G. Bego Mohamed El-Far Nicolas Chomont Alan L. Landay Éric A. Cohen Cécile Tremblay Petronela Ancuta |
| author_facet | Tomas Raul Wiche Salinas Annie Gosselin Laurence Raymond Marchand Etiene Moreira Gabriel Olivier Tastet Jean-Philippe Goulet Yuwei Zhang Dragos Vlad Hanane Touil Jean-Pierre Routy Mariana G. Bego Mohamed El-Far Nicolas Chomont Alan L. Landay Éric A. Cohen Cécile Tremblay Petronela Ancuta |
| author_sort | Tomas Raul Wiche Salinas |
| collection | DOAJ |
| description | Summary: The crosstalk between intestinal epithelial cells (IECs) and Th17-polarized CD4+ T cells is critical for mucosal homeostasis, with HIV-1 causing significant alterations in people living with HIV (PLWH) despite antiretroviral therapy (ART). In a model of IEC and T cell co-cultures, we investigated the effects of IL-17A, the Th17 hallmark cytokine, on IEC ability to promote de novo HIV infection and viral reservoir reactivation. Our results demonstrate that IL-17A acts in synergy with TNF to boost IEC production of CCL20, a Th17-attractant chemokine, and promote HIV trans-infection of CD4+ T cells and viral outgrowth from reservoir cells of ART-treated PLWH. Importantly, the Illumina RNA-sequencing revealed an IL-17A-mediated pro-inflammatory and pro-viral molecular signature, including a decreased expression of type I interferon (IFN-I)-induced HIV restriction factors. These findings point to the deleterious features of IL-17A and raise awareness for caution when designing therapies aimed at restoring the paucity of mucosal Th17 cells in ART-treated PLWH. |
| first_indexed | 2024-12-20T22:41:08Z |
| format | Article |
| id | doaj.art-11fcfb2c9afd4ce1af686fd523cb4e06 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-20T22:41:08Z |
| publishDate | 2021-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-11fcfb2c9afd4ce1af686fd523cb4e062022-12-21T19:24:27ZengElsevieriScience2589-00422021-11-012411103225IL-17A reprograms intestinal epithelial cells to facilitate HIV-1 replication and outgrowth in CD4+ T cellsTomas Raul Wiche Salinas0Annie Gosselin1Laurence Raymond Marchand2Etiene Moreira Gabriel3Olivier Tastet4Jean-Philippe Goulet5Yuwei Zhang6Dragos Vlad7Hanane Touil8Jean-Pierre Routy9Mariana G. Bego10Mohamed El-Far11Nicolas Chomont12Alan L. Landay13Éric A. Cohen14Cécile Tremblay15Petronela Ancuta16CHUM-Research Centre, 900 rue Saint-Denis, Tour Viger R, room R09.416, Montreal, QC H2X 0A9, Canada; Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, CanadaCHUM-Research Centre, 900 rue Saint-Denis, Tour Viger R, room R09.416, Montreal, QC H2X 0A9, CanadaCHUM-Research Centre, 900 rue Saint-Denis, Tour Viger R, room R09.416, Montreal, QC H2X 0A9, CanadaCHUM-Research Centre, 900 rue Saint-Denis, Tour Viger R, room R09.416, Montreal, QC H2X 0A9, Canada; Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, CanadaCHUM-Research Centre, 900 rue Saint-Denis, Tour Viger R, room R09.416, Montreal, QC H2X 0A9, CanadaCaprion, Montréal, QC, CanadaCHUM-Research Centre, 900 rue Saint-Denis, Tour Viger R, room R09.416, Montreal, QC H2X 0A9, CanadaCHUM-Research Centre, 900 rue Saint-Denis, Tour Viger R, room R09.416, Montreal, QC H2X 0A9, CanadaCHUM-Research Centre, 900 rue Saint-Denis, Tour Viger R, room R09.416, Montreal, QC H2X 0A9, Canada; Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, CanadaChronic Viral Illness Service and Division of Hematology, Research Institute of the McGill University Health Centre, Montreal, QC, CanadaDépartement de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, Canada; Institut de Recherches Cliniques de Montréal, Montréal, QC, CanadaCHUM-Research Centre, 900 rue Saint-Denis, Tour Viger R, room R09.416, Montreal, QC H2X 0A9, CanadaCHUM-Research Centre, 900 rue Saint-Denis, Tour Viger R, room R09.416, Montreal, QC H2X 0A9, Canada; Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, CanadaDepartment of Internal Medicine, Rush University Medical Center, Chicago, IL, USADépartement de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, Canada; Institut de Recherches Cliniques de Montréal, Montréal, QC, CanadaCHUM-Research Centre, 900 rue Saint-Denis, Tour Viger R, room R09.416, Montreal, QC H2X 0A9, Canada; Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, CanadaCHUM-Research Centre, 900 rue Saint-Denis, Tour Viger R, room R09.416, Montreal, QC H2X 0A9, Canada; Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, Canada; Corresponding authorSummary: The crosstalk between intestinal epithelial cells (IECs) and Th17-polarized CD4+ T cells is critical for mucosal homeostasis, with HIV-1 causing significant alterations in people living with HIV (PLWH) despite antiretroviral therapy (ART). In a model of IEC and T cell co-cultures, we investigated the effects of IL-17A, the Th17 hallmark cytokine, on IEC ability to promote de novo HIV infection and viral reservoir reactivation. Our results demonstrate that IL-17A acts in synergy with TNF to boost IEC production of CCL20, a Th17-attractant chemokine, and promote HIV trans-infection of CD4+ T cells and viral outgrowth from reservoir cells of ART-treated PLWH. Importantly, the Illumina RNA-sequencing revealed an IL-17A-mediated pro-inflammatory and pro-viral molecular signature, including a decreased expression of type I interferon (IFN-I)-induced HIV restriction factors. These findings point to the deleterious features of IL-17A and raise awareness for caution when designing therapies aimed at restoring the paucity of mucosal Th17 cells in ART-treated PLWH.http://www.sciencedirect.com/science/article/pii/S2589004221011937ImmunologyImmune responseVirology |
| spellingShingle | Tomas Raul Wiche Salinas Annie Gosselin Laurence Raymond Marchand Etiene Moreira Gabriel Olivier Tastet Jean-Philippe Goulet Yuwei Zhang Dragos Vlad Hanane Touil Jean-Pierre Routy Mariana G. Bego Mohamed El-Far Nicolas Chomont Alan L. Landay Éric A. Cohen Cécile Tremblay Petronela Ancuta IL-17A reprograms intestinal epithelial cells to facilitate HIV-1 replication and outgrowth in CD4+ T cells iScience Immunology Immune response Virology |
| title | IL-17A reprograms intestinal epithelial cells to facilitate HIV-1 replication and outgrowth in CD4+ T cells |
| title_full | IL-17A reprograms intestinal epithelial cells to facilitate HIV-1 replication and outgrowth in CD4+ T cells |
| title_fullStr | IL-17A reprograms intestinal epithelial cells to facilitate HIV-1 replication and outgrowth in CD4+ T cells |
| title_full_unstemmed | IL-17A reprograms intestinal epithelial cells to facilitate HIV-1 replication and outgrowth in CD4+ T cells |
| title_short | IL-17A reprograms intestinal epithelial cells to facilitate HIV-1 replication and outgrowth in CD4+ T cells |
| title_sort | il 17a reprograms intestinal epithelial cells to facilitate hiv 1 replication and outgrowth in cd4 t cells |
| topic | Immunology Immune response Virology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221011937 |
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