1. PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease
- Author
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Maite Duhalde Vega, Daniela Olivera, Gustavo Gastão Davanzo, Mauricio Bertullo, Verónica Noya, Gabriela Fabiano de Souza, Stéfanie Primon Muraro, Icaro Castro, Ana Paula Arévalo, Martina Crispo, Germán Galliussi, Sofía Russo, David Charbonnier, Florencia Rammauro, Mathías Jeldres, Catalina Alamón, Valentina Varela, Carlos Batthyany, Mariela Bollati-Fogolín, Pablo Oppezzo, Otto Pritsch, José Luiz Proença-Módena, Helder I. Nakaya, Emiliano Trias, Luis Barbeito, Ignacio Anegon, María Cristina Cuturi, Pedro Moraes-Vieira, Mercedes Segovia, Marcelo Hill, KERANDEL-DION, Céline, Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP), University of the Republic of Uruguay, Universidade Estadual de Campinas = University of Campinas (UNICAMP), CASMU [Montevideo, Uruguay], Sanatorio Americano [Montevideo, Uruguay] (SA), Hospital Israelita Albert Einstein [São Paulo, Brazil], Immunoregulation and Inflamation / Inmunoregulación e Inflamación [Montevideo], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Department of Immunobiology [Montevideo, Uruguay], Universidad de la República [Montevideo] (UDELAR), Team 2 : Cell and gene engineering in tolerance, fertility and regenerative medicine (U1064 Inserm - CR2TI), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)
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[SDV] Life Sciences [q-bio] ,Multidisciplinary ,[SDV]Life Sciences [q-bio] - 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.
- Published
- 2022
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