Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to immune evasion
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
- Location
-
Deutsche Nationalbibliothek Frankfurt am Main
- Extent
-
Online-Ressource
- Language
-
Englisch
- Notes
-
eLife. - 10 (2021) , e59350, ISSN: 2050-084X
- Event
-
Veröffentlichung
- (where)
-
Freiburg
- (who)
-
Universität
- (when)
-
2021
- Creator
-
Angulo, Guillem
Železnjak, Jelena
Martínez-Vicente, Pablo
Puñet-Ortiz, Joan
Hengel, Hartmut
Messerle, Martin
Oxenius, Annette
Jonjic, Stipan
Krmpotić, Astrid
Engel, Pablo
Angulo, Ana
- DOI
-
10.7554/eLife.59350
- URN
-
urn:nbn:de:bsz:25-freidok-1764348
- Rights
-
Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
-
15.08.2025, 7:21 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Angulo, Guillem
- Železnjak, Jelena
- Martínez-Vicente, Pablo
- Puñet-Ortiz, Joan
- Hengel, Hartmut
- Messerle, Martin
- Oxenius, Annette
- Jonjic, Stipan
- Krmpotić, Astrid
- Engel, Pablo
- Angulo, Ana
- Universität
Time of origin
- 2021
Other Objects (12)
Promyelocytic leukemia protein potently restricts human cytomegalovirus infection in endothelial cells
Cytomegalovirus immune evasion sets the functional avidity threshold for protection by CD8 T cells
Tetherin restricts direct cell-to-cell infection of HIV-1
Host factors contributing to human cytomegalovirus infection
E‐Cadherin restricts mast cell degranulation in mice
Tetherin restricts direct cell-cell viral transfer and transmission of HIV-1
Valproic acid restricts mast cell activation by Listeria monocytogenes
The T-cell repertoire specific for the IE-1 protein of human cytomegalovirus : diversity, function and evasion
The T cell repertoire specific for the IE-1 protein of human cytomegalovirus : diversity, function and evasion
Selective receptor expression restricts Nipah virus infection of endothelial cells
LOXL1 promotes tumor cell malignancy and restricts CD8 + T cell infiltration in colorectal cancer
Maf expression in B cells restricts reactive plasmablast and germinal center B cell expansion
Promyelocytic leukemia protein potently restricts human cytomegalovirus infection in endothelial cells
Cytomegalovirus immune evasion sets the functional avidity threshold for protection by CD8 T cells
Tetherin restricts direct cell-to-cell infection of HIV-1
Host factors contributing to human cytomegalovirus infection
E‐Cadherin restricts mast cell degranulation in mice
Tetherin restricts direct cell-cell viral transfer and transmission of HIV-1
Valproic acid restricts mast cell activation by Listeria monocytogenes
The T-cell repertoire specific for the IE-1 protein of human cytomegalovirus : diversity, function and evasion
The T cell repertoire specific for the IE-1 protein of human cytomegalovirus : diversity, function and evasion
Selective receptor expression restricts Nipah virus infection of endothelial cells
LOXL1 promotes tumor cell malignancy and restricts CD8 + T cell infiltration in colorectal cancer
Maf expression in B cells restricts reactive plasmablast and germinal center B cell expansion
Promyelocytic leukemia protein potently restricts human cytomegalovirus infection in endothelial cells
Cytomegalovirus immune evasion sets the functional avidity threshold for protection by CD8 T cells
Tetherin restricts direct cell-to-cell infection of HIV-1
Host factors contributing to human cytomegalovirus infection
E‐Cadherin restricts mast cell degranulation in mice
Tetherin restricts direct cell-cell viral transfer and transmission of HIV-1
Valproic acid restricts mast cell activation by Listeria monocytogenes
The T-cell repertoire specific for the IE-1 protein of human cytomegalovirus : diversity, function and evasion
The T cell repertoire specific for the IE-1 protein of human cytomegalovirus : diversity, function and evasion
Selective receptor expression restricts Nipah virus infection of endothelial cells
LOXL1 promotes tumor cell malignancy and restricts CD8 + T cell infiltration in colorectal cancer