Comprehensive immune profiling reveals that Orbivirus infection activates immune checkpoints during acute T cell immunosuppression

Bluetongue virus (BTV) is an arbovirus transmitted by the bite of infected Culicoides midges that affects domestic and wild ruminants producing great economic losses. The infection induces an IFN response, followed by an adaptive immune response that is essential in disease clearance. BTV can noneth...

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Autores: Louloudes-Lázaro, Andrés, Rojas, José M., García García, Isabel, Rodríguez Martín, Daniel, Morel, Esther, Martín, Verónica, Sevilla, Noemí
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/121127
Acceso en línea:https://hdl.handle.net/20.500.14352/121127
Access Level:acceso abierto
Palabra clave:616.9
579.2
577.27
612.017
Orbivirus
T cells
PD-1/PD-L1 checkpoint
Transcriptomic
Monocytes
B cells
Inmunología
Microbiología médica
2412 Inmunología
2420 Virología
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spelling Comprehensive immune profiling reveals that Orbivirus infection activates immune checkpoints during acute T cell immunosuppressionLouloudes-Lázaro, AndrésRojas, José M.García García, IsabelRodríguez Martín, DanielMorel, EstherMartín, VerónicaSevilla, Noemí616.9579.2577.27612.017OrbivirusT cellsPD-1/PD-L1 checkpointTranscriptomicMonocytesB cellsInmunologíaMicrobiología médica2412 Inmunología2420 VirologíaBluetongue virus (BTV) is an arbovirus transmitted by the bite of infected Culicoides midges that affects domestic and wild ruminants producing great economic losses. The infection induces an IFN response, followed by an adaptive immune response that is essential in disease clearance. BTV can nonetheless impair IFN and humoral responses. The main goal of this study was to gain a more detailed understanding of BTV pathogenesis and its effects on immune cell populations. To this end, we combined flow cytometry and transcriptomic analyses of several immune cells at different times post-infection (pi). Four sheep were infected with BTV serotype 8 and blood samples collected at days 0, 3, 7 and 15pi to perform transcriptomic analysis of B-cell marker+, CD4+, CD8+, and CD14+ sorted peripheral mononuclear cells. The maximum number of differentially expressed genes occurred at day 7pi, which coincided with the peak of infection. KEGG pathway enrichment analysis indicated that genes belonging to virus sensing and immune response initiation pathways were enriched at day 3 and 7 pi in all 4 cell population analyzed. Transcriptomic analysis also showed that at day 7pi T cell exhaustion pathway was enriched in CD4+ cells, while CD8+ cells downregulated immune response initiation pathways. T cell functional studies demonstrated that BTV produced an acute inhibition of CD4+ and CD8+ T cell activation at the peak of replication. This coincided with PD-L1 upregulation on the surface of CD4+ and CD8+ T cells as well as monocytes. Taken together, these data indicate that BTV could exploit the PD1/PD-L1 immune checkpoint to impair T cell responses. These findings identify several mechanisms in the interaction between host and BTV, which could help develop better tools to combat the disease.FrontiersUniversidad Complutense de Madrid20232023-01-0120232023-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/121127reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)InglésengMICIN Not available RTI2018-094616-B-100open accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/1211272026-06-02T12:44:21Z
dc.title.none.fl_str_mv Comprehensive immune profiling reveals that Orbivirus infection activates immune checkpoints during acute T cell immunosuppression
title Comprehensive immune profiling reveals that Orbivirus infection activates immune checkpoints during acute T cell immunosuppression
spellingShingle Comprehensive immune profiling reveals that Orbivirus infection activates immune checkpoints during acute T cell immunosuppression
Louloudes-Lázaro, Andrés
616.9
579.2
577.27
612.017
Orbivirus
T cells
PD-1/PD-L1 checkpoint
Transcriptomic
Monocytes
B cells
Inmunología
Microbiología médica
2412 Inmunología
2420 Virología
title_short Comprehensive immune profiling reveals that Orbivirus infection activates immune checkpoints during acute T cell immunosuppression
title_full Comprehensive immune profiling reveals that Orbivirus infection activates immune checkpoints during acute T cell immunosuppression
title_fullStr Comprehensive immune profiling reveals that Orbivirus infection activates immune checkpoints during acute T cell immunosuppression
title_full_unstemmed Comprehensive immune profiling reveals that Orbivirus infection activates immune checkpoints during acute T cell immunosuppression
title_sort Comprehensive immune profiling reveals that Orbivirus infection activates immune checkpoints during acute T cell immunosuppression
dc.creator.none.fl_str_mv Louloudes-Lázaro, Andrés
Rojas, José M.
García García, Isabel
Rodríguez Martín, Daniel
Morel, Esther
Martín, Verónica
Sevilla, Noemí
author Louloudes-Lázaro, Andrés
author_facet Louloudes-Lázaro, Andrés
Rojas, José M.
García García, Isabel
Rodríguez Martín, Daniel
Morel, Esther
Martín, Verónica
Sevilla, Noemí
author_role author
author2 Rojas, José M.
García García, Isabel
Rodríguez Martín, Daniel
Morel, Esther
Martín, Verónica
Sevilla, Noemí
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 616.9
579.2
577.27
612.017
Orbivirus
T cells
PD-1/PD-L1 checkpoint
Transcriptomic
Monocytes
B cells
Inmunología
Microbiología médica
2412 Inmunología
2420 Virología
topic 616.9
579.2
577.27
612.017
Orbivirus
T cells
PD-1/PD-L1 checkpoint
Transcriptomic
Monocytes
B cells
Inmunología
Microbiología médica
2412 Inmunología
2420 Virología
description Bluetongue virus (BTV) is an arbovirus transmitted by the bite of infected Culicoides midges that affects domestic and wild ruminants producing great economic losses. The infection induces an IFN response, followed by an adaptive immune response that is essential in disease clearance. BTV can nonetheless impair IFN and humoral responses. The main goal of this study was to gain a more detailed understanding of BTV pathogenesis and its effects on immune cell populations. To this end, we combined flow cytometry and transcriptomic analyses of several immune cells at different times post-infection (pi). Four sheep were infected with BTV serotype 8 and blood samples collected at days 0, 3, 7 and 15pi to perform transcriptomic analysis of B-cell marker+, CD4+, CD8+, and CD14+ sorted peripheral mononuclear cells. The maximum number of differentially expressed genes occurred at day 7pi, which coincided with the peak of infection. KEGG pathway enrichment analysis indicated that genes belonging to virus sensing and immune response initiation pathways were enriched at day 3 and 7 pi in all 4 cell population analyzed. Transcriptomic analysis also showed that at day 7pi T cell exhaustion pathway was enriched in CD4+ cells, while CD8+ cells downregulated immune response initiation pathways. T cell functional studies demonstrated that BTV produced an acute inhibition of CD4+ and CD8+ T cell activation at the peak of replication. This coincided with PD-L1 upregulation on the surface of CD4+ and CD8+ T cells as well as monocytes. Taken together, these data indicate that BTV could exploit the PD1/PD-L1 immune checkpoint to impair T cell responses. These findings identify several mechanisms in the interaction between host and BTV, which could help develop better tools to combat the disease.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-01-01
2023
2023-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/121127
url https://hdl.handle.net/20.500.14352/121127
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv MICIN Not available RTI2018-094616-B-100
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers
publisher.none.fl_str_mv Frontiers
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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