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http://hdl.handle.net/2445/195421
Title: | Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to immune evasion |
Author: | Angulo, Guillem Zeleznjak, Jelena Martínez Vicente, Pablo Puñet Ortiz, Joan Hengel, Hartmut Messerle, Martin Oxenius, Annette Jonjic, Stipan Krmpotić, Astrid Engel Rocamora, Pablo Angulo Aguado, Ana |
Keywords: | Antígens Citomegalovirus Herpesvirus Immunitat cel·lular Inflamació Cèl·lules T Malalties víriques Ratolins (Animals de laboratori) Antigens Cytomegaloviruses Herpesviruses Cellular immunity Inflammation T cells Virus diseases Mice (Laboratory animals) |
Issue Date: | 18-Jan-2021 |
Publisher: | eLife Sciences |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.7554/eLife.59350 |
It is part of: | eLife, 2021, vol. 10, num. e59350 |
URI: | http://hdl.handle.net/2445/195421 |
Related resource: | https://doi.org/10.7554/eLife.59350 |
ISSN: | 2050-084X |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Biomedicina) |
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