Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to immune evasion
Viral infections are controlled, and very often cleared, by activated T lymphocytes. The inducible co-stimulator (ICOS) mediates its functions by binding to its ligand ICOSL, enhancing T-cell activation and optimal germinal center (GC) formation. Here, we show that ICOSL is heavily downmodulated dur...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/59350 |
| _version_ | 1811180582432931840 |
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| author | Guillem Angulo Jelena Zeleznjak Pablo Martínez-Vicente Joan Puñet-Ortiz Hartmut Hengel Martin Messerle Annette Oxenius Stipan Jonjic Astrid Krmpotić Pablo Engel Ana Angulo |
| author_facet | Guillem Angulo Jelena Zeleznjak Pablo Martínez-Vicente Joan Puñet-Ortiz Hartmut Hengel Martin Messerle Annette Oxenius Stipan Jonjic Astrid Krmpotić Pablo Engel Ana Angulo |
| author_sort | Guillem Angulo |
| collection | DOAJ |
| description | Viral infections are controlled, and very often cleared, by activated T lymphocytes. The inducible co-stimulator (ICOS) mediates its functions by binding to its ligand ICOSL, enhancing T-cell activation and optimal germinal center (GC) formation. Here, we show that ICOSL is heavily downmodulated during infection of antigen-presenting cells by different herpesviruses. We found that, in murine cytomegalovirus (MCMV), the immunoevasin m138/fcr-1 physically interacts with ICOSL, impeding its maturation and promoting its lysosomal degradation. This viral protein counteracts T-cell responses, in an ICOS-dependent manner, and limits virus control during the acute MCMV infection. Additionally, we report that blockade of ICOSL in MCMV-infected mice critically regulates the production of MCMV-specific antibodies due to a reduction of T follicular helper and GC B cells. Altogether, these findings reveal a novel mechanism evolved by MCMV to counteract adaptive immune surveillance, and demonstrates a role of the ICOS:ICOSL axis in the host defense against herpesviruses. |
| first_indexed | 2024-04-11T09:05:35Z |
| format | Article |
| id | doaj.art-fbe9d28751254e9a9fb777c86be9f73d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:05:35Z |
| publishDate | 2021-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-fbe9d28751254e9a9fb777c86be9f73d2022-12-22T04:32:39ZengeLife Sciences Publications LtdeLife2050-084X2021-01-011010.7554/eLife.59350Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to immune evasionGuillem Angulo0https://orcid.org/0000-0001-7086-9754Jelena Zeleznjak1https://orcid.org/0000-0001-6619-3675Pablo Martínez-Vicente2https://orcid.org/0000-0001-9277-1950Joan Puñet-Ortiz3Hartmut Hengel4https://orcid.org/0000-0002-3482-816XMartin Messerle5Annette Oxenius6Stipan Jonjic7Astrid Krmpotić8Pablo Engel9https://orcid.org/0000-0001-8410-252XAna Angulo10https://orcid.org/0000-0002-5792-1164Immunology Unit, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, SpainCenter for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, CroatiaImmunology Unit, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, SpainImmunology Unit, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, SpainInstitute of Virology, University Medical Center, Albert-Ludwigs-University Freiburg, Freiburg, Germany; Faculty of Medicine, Albert-Ludwigs-University Freiburg, Freiburg, GermanyInstitute of Virology, Hannover Medical School, Hannover, GermanyInstitute of Microbiology, Department of Biology, ETH Zürich, Zürich, SwitzerlandCenter for Proteomics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia; Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, CroatiaDepartment of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, CroatiaImmunology Unit, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, SpainImmunology Unit, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, SpainViral infections are controlled, and very often cleared, by activated T lymphocytes. The inducible co-stimulator (ICOS) mediates its functions by binding to its ligand ICOSL, enhancing T-cell activation and optimal germinal center (GC) formation. Here, we show that ICOSL is heavily downmodulated during infection of antigen-presenting cells by different herpesviruses. We found that, in murine cytomegalovirus (MCMV), the immunoevasin m138/fcr-1 physically interacts with ICOSL, impeding its maturation and promoting its lysosomal degradation. This viral protein counteracts T-cell responses, in an ICOS-dependent manner, and limits virus control during the acute MCMV infection. Additionally, we report that blockade of ICOSL in MCMV-infected mice critically regulates the production of MCMV-specific antibodies due to a reduction of T follicular helper and GC B cells. Altogether, these findings reveal a novel mechanism evolved by MCMV to counteract adaptive immune surveillance, and demonstrates a role of the ICOS:ICOSL axis in the host defense against herpesviruses.https://elifesciences.org/articles/59350cytomegalovirusherpesvirust-cell co-stimulationicoslcd275viral immune evasion |
| spellingShingle | Guillem Angulo Jelena Zeleznjak Pablo Martínez-Vicente Joan Puñet-Ortiz Hartmut Hengel Martin Messerle Annette Oxenius Stipan Jonjic Astrid Krmpotić Pablo Engel Ana Angulo Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to immune evasion eLife cytomegalovirus herpesvirus t-cell co-stimulation icosl cd275 viral immune evasion |
| title | Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to immune evasion |
| title_full | Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to immune evasion |
| title_fullStr | Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to immune evasion |
| title_full_unstemmed | Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to immune evasion |
| title_short | Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to immune evasion |
| title_sort | cytomegalovirus restricts icosl expression on antigen presenting cells disabling t cell co stimulation and contributing to immune evasion |
| topic | cytomegalovirus herpesvirus t-cell co-stimulation icosl cd275 viral immune evasion |
| url | https://elifesciences.org/articles/59350 |
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