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2021-01-18

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cc-by (c) Angulo, Guillem et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/195421

Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to immune evasion

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Recurs relacionat

https://doi.org/10.7554/eLife.59350

Resum

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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Matèries

Antígens, Citomegalovirus, Herpesvirus, Immunitat cel·lular, Inflamació, Cèl·lules T, Malalties víriques, Ratolins (Animals de laboratori)

Matèries (anglès)

Antigens, Cytomegaloviruses, Herpesviruses, Cellular immunity, Inflammation, T cells, Virus diseases, Mice (Laboratory animals)

Citació

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Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Citació

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. Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to immune evasion. _eLife_. 2021. Vol. 10, núm. e59350. [consulta: 11 de desembre de 2025]. ISSN: 2050-084X. [Disponible a: https://hdl.handle.net/2445/195421]

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