Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840182/ https://www.ncbi.nlm.nih.gov/pubmed/33459589 http://dx.doi.org/10.7554/eLife.59350 |
_version_ | 1783643522956525568 |
---|---|
author | Angulo, Guillem Zeleznjak, Jelena Martínez-Vicente, Pablo Puñet-Ortiz, Joan Hengel, Hartmut Messerle, Martin Oxenius, Annette Jonjic, Stipan Krmpotić, Astrid Engel, Pablo Angulo, Ana |
author_facet | Angulo, Guillem Zeleznjak, Jelena Martínez-Vicente, Pablo Puñet-Ortiz, Joan Hengel, Hartmut Messerle, Martin Oxenius, Annette Jonjic, Stipan Krmpotić, Astrid Engel, Pablo Angulo, Ana |
author_sort | Angulo, Guillem |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7840182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-78401822021-02-01 Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to immune evasion Angulo, Guillem Zeleznjak, Jelena Martínez-Vicente, Pablo Puñet-Ortiz, Joan Hengel, Hartmut Messerle, Martin Oxenius, Annette Jonjic, Stipan Krmpotić, Astrid Engel, Pablo Angulo, Ana eLife Immunology and Inflammation 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. eLife Sciences Publications, Ltd 2021-01-18 /pmc/articles/PMC7840182/ /pubmed/33459589 http://dx.doi.org/10.7554/eLife.59350 Text en © 2021, Angulo et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Angulo, Guillem Zeleznjak, Jelena Martínez-Vicente, Pablo Puñet-Ortiz, Joan Hengel, Hartmut Messerle, Martin Oxenius, Annette Jonjic, Stipan Krmpotić, Astrid Engel, Pablo Angulo, Ana Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to 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 | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840182/ https://www.ncbi.nlm.nih.gov/pubmed/33459589 http://dx.doi.org/10.7554/eLife.59350 |
work_keys_str_mv | AT anguloguillem cytomegalovirusrestrictsicoslexpressiononantigenpresentingcellsdisablingtcellcostimulationandcontributingtoimmuneevasion AT zeleznjakjelena cytomegalovirusrestrictsicoslexpressiononantigenpresentingcellsdisablingtcellcostimulationandcontributingtoimmuneevasion AT martinezvicentepablo cytomegalovirusrestrictsicoslexpressiononantigenpresentingcellsdisablingtcellcostimulationandcontributingtoimmuneevasion AT punetortizjoan cytomegalovirusrestrictsicoslexpressiononantigenpresentingcellsdisablingtcellcostimulationandcontributingtoimmuneevasion AT hengelhartmut cytomegalovirusrestrictsicoslexpressiononantigenpresentingcellsdisablingtcellcostimulationandcontributingtoimmuneevasion AT messerlemartin cytomegalovirusrestrictsicoslexpressiononantigenpresentingcellsdisablingtcellcostimulationandcontributingtoimmuneevasion AT oxeniusannette cytomegalovirusrestrictsicoslexpressiononantigenpresentingcellsdisablingtcellcostimulationandcontributingtoimmuneevasion AT jonjicstipan cytomegalovirusrestrictsicoslexpressiononantigenpresentingcellsdisablingtcellcostimulationandcontributingtoimmuneevasion AT krmpoticastrid cytomegalovirusrestrictsicoslexpressiononantigenpresentingcellsdisablingtcellcostimulationandcontributingtoimmuneevasion AT engelpablo cytomegalovirusrestrictsicoslexpressiononantigenpresentingcellsdisablingtcellcostimulationandcontributingtoimmuneevasion AT anguloana cytomegalovirusrestrictsicoslexpressiononantigenpresentingcellsdisablingtcellcostimulationandcontributingtoimmuneevasion |