PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease

Autores: Duhalde Vega, Maite; Olivera, Daniela; Davanzo, Gustavo Gastão; Bertullo, Mauricio; Noya, Verónica; de Souza, Gabriela Fabiano; Muraro, Stéfanie Primon; Castro, Icaro; Arévalo, Ana Paula; Crispo, Martina; Galliussi, Germán; Russo, Sofía; Charbonnier, David; Rammauro, Florencia; Jeldres, Mathías; Alamón, Catalina; Varela, Valentina; Batthyany, Carlos; Bollati Fogolín, Mariela; Oppezzo, Pablo; Pritsch, Otto; Proença Módena, José Luiz; Nakaya, Helder I.; Trias, Emiliano; Barbeito, Luis; Anegon, Ignacio; Cuturi, María Cristina; Moraes Vieira, Pedro; Segovia, Mercedes; Hill, Marcelo
Año de publicación: 2022
Idioma: inglés
Tipo de recurso: artículo
Estado: versión publicada
Descripción: Severe COVID-19 is associated with hyperinflammation and weak T cell responses against SARS-CoV-2. However, the links between those processes remain partially characterized. Moreover, whether and how therapeutically manipulating T cells may benefit patients are unknown. Our genetic and pharmacological evidence demonstrates that the ion channel TMEM176B inhibited inflammasome activation triggered by SARS-CoV-2 and SARS-CoV-2- related murine β-coronavirus. Tmem176b-/- mice infected with murine β-coronavirus developed inflammasome-dependent T cell dysfunction and critical disease, which was controlled by modulating dysfunctional T cells with PD-1 blockers. In critical COVID-19, inflammasome activation correlated with dysfunctional T cells and low monocytic TMEM176B expression, whereas PD-L1 blockade rescued T cell functionality. Here, we mechanistically link T cell dysfunction and inflammation, supporting a cancer immunotherapy to reinforce T cell immunity in critical β-coronavirus disease.
Fil: Duhalde Vega, Maite. Institut Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Olivera, Daniela. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
Fil: Davanzo, Gustavo Gastão. Universidade Estadual de Campinas; Brasil
Fil: Bertullo, Mauricio. Immunoregulation And Inflammation Lab; Uruguay
Fil: Noya, Verónica. Sanatorio Americano; Uruguay
Fil: de Souza, Gabriela Fabiano. Universidade Estadual de Campinas; Brasil
Fil: Muraro, Stéfanie Primon. Universidade Estadual de Campinas; Brasil
Fil: Castro, Icaro. Hospital Israelita Albert Einstein; Brasil
Fil: Arévalo, Ana Paula. Institut Pasteur de Montevideo; Uruguay
Fil: Crispo, Martina. Institut Pasteur de Montevideo; Uruguay
Fil: Galliussi, Germán. Institut Pasteur de Montevideo; Uruguay
Fil: Russo, Sofía. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
Fil: Charbonnier, David. Institut Pasteur de Montevideo; Uruguay
Fil: Rammauro, Florencia. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
Fil: Jeldres, Mathías. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
Fil: Alamón, Catalina. Institut Pasteur de Montevideo; Uruguay
Fil: Varela, Valentina. Institut Pasteur de Montevideo; Uruguay
Fil: Batthyany, Carlos. Institut Pasteur de Montevideo; Uruguay
Fil: Bollati Fogolín, Mariela. Institut Pasteur de Montevideo; Uruguay
Fil: Oppezzo, Pablo. Institut Pasteur de Montevideo; Uruguay
Fil: Pritsch, Otto. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
Fil: Proença Módena, José Luiz. Universidade Estadual de Campinas; Brasil
Fil: Nakaya, Helder I.. Hospital Israelita Albert Einstein; Brasil
Fil: Trias, Emiliano. Institut Pasteur de Montevideo; Uruguay
Fil: Barbeito, Luis. Institut Pasteur de Montevideo; Uruguay
Fil: Anegon, Ignacio. Center For Research In Transplantation And Immunology; Francia
Fil: Cuturi, María Cristina. Center For Research In Transplantation And Immunology; Francia
Fil: Moraes Vieira, Pedro. Universidade Estadual de Campinas; Brasil
Fil: Segovia, Mercedes. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay
Fil: Hill, Marcelo. Universidad de la República; Uruguay. Institut Pasteur de Montevideo; Uruguay
Materia: COVID-19
Inflamasoma
PDL1
TORID
Nivel de accesibilidad: acceso abierto
Condiciones de uso: https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
Institución: Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador: oai:ri.conicet.gov.ar:11336/215641

Acceder

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oai_identifier_str	oai:ri.conicet.gov.ar:11336/215641
network_acronym_str	CONICETDig
repository_id_str	3498
network_name_str	CONICET Digital (CONICET)
spelling	PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus diseaseDuhalde Vega, MaiteOlivera, DanielaDavanzo, Gustavo GastãoBertullo, MauricioNoya, Verónicade Souza, Gabriela FabianoMuraro, Stéfanie PrimonCastro, IcaroArévalo, Ana PaulaCrispo, MartinaGalliussi, GermánRusso, SofíaCharbonnier, DavidRammauro, FlorenciaJeldres, MathíasAlamón, CatalinaVarela, ValentinaBatthyany, CarlosBollati Fogolín, MarielaOppezzo, PabloPritsch, OttoProença Módena, José LuizNakaya, Helder I.Trias, EmilianoBarbeito, LuisAnegon, IgnacioCuturi, María CristinaMoraes Vieira, PedroSegovia, MercedesHill, MarceloCOVID-19InflamasomaPDL1TORIDhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Severe COVID-19 is associated with hyperinflammation and weak T cell responses against SARS-CoV-2. However, the links between those processes remain partially characterized. Moreover, whether and how therapeutically manipulating T cells may benefit patients are unknown. Our genetic and pharmacological evidence demonstrates that the ion channel TMEM176B inhibited inflammasome activation triggered by SARS-CoV-2 and SARS-CoV-2- related murine β-coronavirus. Tmem176b-/- mice infected with murine β-coronavirus developed inflammasome-dependent T cell dysfunction and critical disease, which was controlled by modulating dysfunctional T cells with PD-1 blockers. In critical COVID-19, inflammasome activation correlated with dysfunctional T cells and low monocytic TMEM176B expression, whereas PD-L1 blockade rescued T cell functionality. Here, we mechanistically link T cell dysfunction and inflammation, supporting a cancer immunotherapy to reinforce T cell immunity in critical β-coronavirus disease.Fil: Duhalde Vega, Maite. Institut Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Olivera, Daniela. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Davanzo, Gustavo Gastão. Universidade Estadual de Campinas; BrasilFil: Bertullo, Mauricio. Immunoregulation And Inflammation Lab; UruguayFil: Noya, Verónica. Sanatorio Americano; UruguayFil: de Souza, Gabriela Fabiano. Universidade Estadual de Campinas; BrasilFil: Muraro, Stéfanie Primon. Universidade Estadual de Campinas; BrasilFil: Castro, Icaro. Hospital Israelita Albert Einstein; BrasilFil: Arévalo, Ana Paula. Institut Pasteur de Montevideo; UruguayFil: Crispo, Martina. Institut Pasteur de Montevideo; UruguayFil: Galliussi, Germán. Institut Pasteur de Montevideo; UruguayFil: Russo, Sofía. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Charbonnier, David. Institut Pasteur de Montevideo; UruguayFil: Rammauro, Florencia. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Jeldres, Mathías. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Alamón, Catalina. Institut Pasteur de Montevideo; UruguayFil: Varela, Valentina. Institut Pasteur de Montevideo; UruguayFil: Batthyany, Carlos. Institut Pasteur de Montevideo; UruguayFil: Bollati Fogolín, Mariela. Institut Pasteur de Montevideo; UruguayFil: Oppezzo, Pablo. Institut Pasteur de Montevideo; UruguayFil: Pritsch, Otto. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Proença Módena, José Luiz. Universidade Estadual de Campinas; BrasilFil: Nakaya, Helder I.. Hospital Israelita Albert Einstein; BrasilFil: Trias, Emiliano. Institut Pasteur de Montevideo; UruguayFil: Barbeito, Luis. Institut Pasteur de Montevideo; UruguayFil: Anegon, Ignacio. Center For Research In Transplantation And Immunology; FranciaFil: Cuturi, María Cristina. Center For Research In Transplantation And Immunology; FranciaFil: Moraes Vieira, Pedro. Universidade Estadual de Campinas; BrasilFil: Segovia, Mercedes. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; UruguayFil: Hill, Marcelo. Universidad de la República; Uruguay. Institut Pasteur de Montevideo; UruguayScience Advances is the American Association for the Advancement of Science2022-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/215641Duhalde Vega, Maite; Olivera, Daniela; Davanzo, Gustavo Gastão; Bertullo, Mauricio; Noya, Verónica; et al.; PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease; Science Advances is the American Association for the Advancement of Science; Science Advances; 8; 38; 9-2022; 1-142375-2548CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.science.org/doi/10.1126/sciadv.abn6545info:eu-repo/semantics/altIdentifier/doi/10.1126/sciadv.abn6545info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:27:45Zoai:ri.conicet.gov.ar:11336/215641instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:27:46.131CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv	PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease
title	PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease
spellingShingle	PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease Duhalde Vega, Maite COVID-19 Inflamasoma PDL1 TORID
title_short	PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease
title_full	PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease
title_fullStr	PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease
title_full_unstemmed	PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease
title_sort	PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease
dc.creator.none.fl_str_mv	Duhalde Vega, Maite Olivera, Daniela Davanzo, Gustavo Gastão Bertullo, Mauricio Noya, Verónica de Souza, Gabriela Fabiano Muraro, Stéfanie Primon Castro, Icaro Arévalo, Ana Paula Crispo, Martina Galliussi, Germán Russo, Sofía Charbonnier, David Rammauro, Florencia Jeldres, Mathías Alamón, Catalina Varela, Valentina Batthyany, Carlos Bollati Fogolín, Mariela Oppezzo, Pablo Pritsch, Otto Proença Módena, José Luiz Nakaya, Helder I. Trias, Emiliano Barbeito, Luis Anegon, Ignacio Cuturi, María Cristina Moraes Vieira, Pedro Segovia, Mercedes Hill, Marcelo
author	Duhalde Vega, Maite
author_facet	Duhalde Vega, Maite Olivera, Daniela Davanzo, Gustavo Gastão Bertullo, Mauricio Noya, Verónica de Souza, Gabriela Fabiano Muraro, Stéfanie Primon Castro, Icaro Arévalo, Ana Paula Crispo, Martina Galliussi, Germán Russo, Sofía Charbonnier, David Rammauro, Florencia Jeldres, Mathías Alamón, Catalina Varela, Valentina Batthyany, Carlos Bollati Fogolín, Mariela Oppezzo, Pablo Pritsch, Otto Proença Módena, José Luiz Nakaya, Helder I. Trias, Emiliano Barbeito, Luis Anegon, Ignacio Cuturi, María Cristina Moraes Vieira, Pedro Segovia, Mercedes Hill, Marcelo
author_role	author
author2	Olivera, Daniela Davanzo, Gustavo Gastão Bertullo, Mauricio Noya, Verónica de Souza, Gabriela Fabiano Muraro, Stéfanie Primon Castro, Icaro Arévalo, Ana Paula Crispo, Martina Galliussi, Germán Russo, Sofía Charbonnier, David Rammauro, Florencia Jeldres, Mathías Alamón, Catalina Varela, Valentina Batthyany, Carlos Bollati Fogolín, Mariela Oppezzo, Pablo Pritsch, Otto Proença Módena, José Luiz Nakaya, Helder I. Trias, Emiliano Barbeito, Luis Anegon, Ignacio Cuturi, María Cristina Moraes Vieira, Pedro Segovia, Mercedes Hill, Marcelo
author2_role	author author author author author author author author author author author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	COVID-19 Inflamasoma PDL1 TORID
topic	COVID-19 Inflamasoma PDL1 TORID
purl_subject.fl_str_mv	https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv	Severe COVID-19 is associated with hyperinflammation and weak T cell responses against SARS-CoV-2. However, the links between those processes remain partially characterized. Moreover, whether and how therapeutically manipulating T cells may benefit patients are unknown. Our genetic and pharmacological evidence demonstrates that the ion channel TMEM176B inhibited inflammasome activation triggered by SARS-CoV-2 and SARS-CoV-2- related murine β-coronavirus. Tmem176b-/- mice infected with murine β-coronavirus developed inflammasome-dependent T cell dysfunction and critical disease, which was controlled by modulating dysfunctional T cells with PD-1 blockers. In critical COVID-19, inflammasome activation correlated with dysfunctional T cells and low monocytic TMEM176B expression, whereas PD-L1 blockade rescued T cell functionality. Here, we mechanistically link T cell dysfunction and inflammation, supporting a cancer immunotherapy to reinforce T cell immunity in critical β-coronavirus disease. Fil: Duhalde Vega, Maite. Institut Pasteur de Montevideo; Uruguay. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina Fil: Olivera, Daniela. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay Fil: Davanzo, Gustavo Gastão. Universidade Estadual de Campinas; Brasil Fil: Bertullo, Mauricio. Immunoregulation And Inflammation Lab; Uruguay Fil: Noya, Verónica. Sanatorio Americano; Uruguay Fil: de Souza, Gabriela Fabiano. Universidade Estadual de Campinas; Brasil Fil: Muraro, Stéfanie Primon. Universidade Estadual de Campinas; Brasil Fil: Castro, Icaro. Hospital Israelita Albert Einstein; Brasil Fil: Arévalo, Ana Paula. Institut Pasteur de Montevideo; Uruguay Fil: Crispo, Martina. Institut Pasteur de Montevideo; Uruguay Fil: Galliussi, Germán. Institut Pasteur de Montevideo; Uruguay Fil: Russo, Sofía. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay Fil: Charbonnier, David. Institut Pasteur de Montevideo; Uruguay Fil: Rammauro, Florencia. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay Fil: Jeldres, Mathías. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay Fil: Alamón, Catalina. Institut Pasteur de Montevideo; Uruguay Fil: Varela, Valentina. Institut Pasteur de Montevideo; Uruguay Fil: Batthyany, Carlos. Institut Pasteur de Montevideo; Uruguay Fil: Bollati Fogolín, Mariela. Institut Pasteur de Montevideo; Uruguay Fil: Oppezzo, Pablo. Institut Pasteur de Montevideo; Uruguay Fil: Pritsch, Otto. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay Fil: Proença Módena, José Luiz. Universidade Estadual de Campinas; Brasil Fil: Nakaya, Helder I.. Hospital Israelita Albert Einstein; Brasil Fil: Trias, Emiliano. Institut Pasteur de Montevideo; Uruguay Fil: Barbeito, Luis. Institut Pasteur de Montevideo; Uruguay Fil: Anegon, Ignacio. Center For Research In Transplantation And Immunology; Francia Fil: Cuturi, María Cristina. Center For Research In Transplantation And Immunology; Francia Fil: Moraes Vieira, Pedro. Universidade Estadual de Campinas; Brasil Fil: Segovia, Mercedes. Institut Pasteur de Montevideo; Uruguay. Universidad de la República; Uruguay Fil: Hill, Marcelo. Universidad de la República; Uruguay. Institut Pasteur de Montevideo; Uruguay
description	Severe COVID-19 is associated with hyperinflammation and weak T cell responses against SARS-CoV-2. However, the links between those processes remain partially characterized. Moreover, whether and how therapeutically manipulating T cells may benefit patients are unknown. Our genetic and pharmacological evidence demonstrates that the ion channel TMEM176B inhibited inflammasome activation triggered by SARS-CoV-2 and SARS-CoV-2- related murine β-coronavirus. Tmem176b-/- mice infected with murine β-coronavirus developed inflammasome-dependent T cell dysfunction and critical disease, which was controlled by modulating dysfunctional T cells with PD-1 blockers. In critical COVID-19, inflammasome activation correlated with dysfunctional T cells and low monocytic TMEM176B expression, whereas PD-L1 blockade rescued T cell functionality. Here, we mechanistically link T cell dysfunction and inflammation, supporting a cancer immunotherapy to reinforce T cell immunity in critical β-coronavirus disease.
publishDate	2022
dc.date.none.fl_str_mv	2022-09
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/11336/215641 Duhalde Vega, Maite; Olivera, Daniela; Davanzo, Gustavo Gastão; Bertullo, Mauricio; Noya, Verónica; et al.; PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease; Science Advances is the American Association for the Advancement of Science; Science Advances; 8; 38; 9-2022; 1-14 2375-2548 CONICET Digital CONICET
url	http://hdl.handle.net/11336/215641
identifier_str_mv	Duhalde Vega, Maite; Olivera, Daniela; Davanzo, Gustavo Gastão; Bertullo, Mauricio; Noya, Verónica; et al.; PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease; Science Advances is the American Association for the Advancement of Science; Science Advances; 8; 38; 9-2022; 1-14 2375-2548 CONICET Digital CONICET
dc.language.none.fl_str_mv	eng
language	eng
dc.relation.none.fl_str_mv	info:eu-repo/semantics/altIdentifier/url/https://www.science.org/doi/10.1126/sciadv.abn6545 info:eu-repo/semantics/altIdentifier/doi/10.1126/sciadv.abn6545
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv	openAccess
rights_invalid_str_mv	https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv	application/pdf application/pdf
dc.publisher.none.fl_str_mv	Science Advances is the American Association for the Advancement of Science
publisher.none.fl_str_mv	Science Advances is the American Association for the Advancement of Science
dc.source.none.fl_str_mv	reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str	CONICET Digital (CONICET)
collection	CONICET Digital (CONICET)
instname_str	Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv	CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv	dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score	13.070432

PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease

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