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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...

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Autores principales: Angulo, Guillem, Zeleznjak, Jelena, Martínez-Vicente, Pablo, Puñet-Ortiz, Joan, Hengel, Hartmut, Messerle, Martin, Oxenius, Annette, Jonjic, Stipan, Krmpotić, Astrid, Engel, Pablo, Angulo, Ana
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
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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.
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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
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