Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to immune evasion.
antigen presenting cells
cd275
cytomegalovirus
herpesvirus
icosl
immunology
inflammation
mouse
t-cell co-stimulation
viral immune evasion
virus
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
18 01 2021
18 01 2021
Historique:
received:
27
05
2020
accepted:
15
01
2021
pubmed:
19
1
2021
medline:
4
2
2022
entrez:
18
1
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33459589
doi: 10.7554/eLife.59350
pii: 59350
pmc: PMC7840182
doi:
pii:
Substances chimiques
Inducible T-Cell Co-Stimulator Ligand
0
Inducible T-Cell Co-Stimulator Protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2021, Angulo et al.
Déclaration de conflit d'intérêts
GA, JZ, PM, JP, HH, MM, AO, AK, PE, AA No competing interests declared, SJ Reviewing editor, eLife
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