PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Science Advances Year : 2022

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

Maite Duhalde Vega
Institut Pasteur de Montevideo
Daniela Olivera
Institut Pasteur de Montevideo
University of the Republic of Uruguay
Gustavo Gastão Davanzo
Universidade Estadual de Campinas = University of Campinas
Mauricio Bertullo
CASMU [Montevideo, Uruguay]
Verónica Noya
Sanatorio Americano [Montevideo, Uruguay]
Gabriela Fabiano de Souza
  • Function : Author
Universidade Estadual de Campinas = University of Campinas
Stéfanie Primon Muraro
Universidade Estadual de Campinas = University of Campinas
Icaro Castro
Hospital Israelita Albert Einstein [São Paulo, Brazil]
Ana Paula Arévalo
Institut Pasteur de Montevideo
Martina Crispo
Institut Pasteur de Montevideo
Germán Galliussi
Institut Pasteur de Montevideo
Sofía Russo
Immunoregulation and Inflamation / Inmunoregulación e Inflamación [Montevideo]
Department of Immunobiology [Montevideo, Uruguay]
Institut Pasteur de Montevideo
University of the Republic of Uruguay
David Charbonnier
Institut Pasteur de Montevideo
Florencia Rammauro
University of the Republic of Uruguay
Mathías Jeldres
Immunoregulation and Inflamation / Inmunoregulación e Inflamación [Montevideo]
University of the Republic of Uruguay
Catalina Alamón
  • Function : Author
Institut Pasteur de Montevideo
Valentina Varela
Institut Pasteur de Montevideo
Carlos Batthyany
  • Function : Author
Institut Pasteur de Montevideo
Mariela Bollati-Fogolín
Institut Pasteur de Montevideo
Pablo Oppezzo
Institut Pasteur de Montevideo
Otto Pritsch
University of the Republic of Uruguay
Institut Pasteur de Montevideo
José Luiz Proença-Módena
Universidade Estadual de Campinas = University of Campinas
Helder Nakaya
Hospital Israelita Albert Einstein [São Paulo, Brazil]
Emiliano Trias
Institut Pasteur de Montevideo
Luis Barbeito
Institut Pasteur de Montevideo
Ignacio Anegon
Team 2 : Cell and gene engineering in tolerance, fertility and regenerative medicine
María Cristina Cuturi
  • Function : Author
Team 2 : Cell and gene engineering in tolerance, fertility and regenerative medicine
Pedro Moraes-Vieira
Universidade Estadual de Campinas = University of Campinas
Mercedes Segovia
Institut Pasteur de Montevideo
University of the Republic of Uruguay
Marcelo Hill
Institut Pasteur de Montevideo
University of the Republic of Uruguay

Abstract

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.

Domains

Life Sciences [q-bio]
Fichier principal
Vignette du fichier
sciadv.abn6545.pdf (669.62 Ko) Télécharger le fichier
Origin : Publication funded by an institution

Céline KERANDEL-DION  : Connect in order to contact the contributor

https://www.hal.inserm.fr/inserm-03872232

Submitted on : Friday, November 25, 2022-3:34:45 PM

Last modification on : Wednesday, May 24, 2023-4:14:17 PM

Long-term archiving on: Sunday, February 26, 2023-7:15:17 PM

Download

Dates and versions

inserm-03872232 , version 1 (25-11-2022)

Identifiers

Cite

Maite Duhalde Vega, Daniela Olivera, Gustavo Gastão Davanzo, Mauricio Bertullo, Verónica Noya, et al.. PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease. Science Advances , 2022, 8 (38), pp.eabn6545. ⟨10.1126/sciadv.abn6545⟩. ⟨inserm-03872232⟩

Export

BibTeX TEI Dublin Core DC Terms EndNote Datacite

Collections

INSERM RIIP RIIP_MONTEVIDEO CRTI NANTES-UNIVERSITE CR2TI UFR-MEDECINE-NANTES
16 View
64 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More