Produção Nacional
Revisado por pares
PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease
2022; American Association for the Advancement of Science; Volume: 8; Issue: 38 Linguagem: Inglês
10.1126/sciadv.abn6545
ISSN2375-2548
AutoresMaite Duhalde Vega, Daniela Olivera, Gustavo Gastão Davanzo, Mauricio Bertullo, Verónica Noya, Gabriela Fabiano de Souza, Stéfanie Primon Muraro, Ícaro Maia Santos de Castro, Ana Paula Arévalo, Martina Crispo, Germán Galliussi, Sofía Russo, David Charbonnier, Florencia Rammauro, Mathías Jeldres, Catalina Alamón, Valentina Varela, Carlos Batthyány, Mariela Bollati‐Fogolín, Pablo Oppezzo, Otto Pritsch, José Luiz Proença‐Módena, Helder I. Nakaya, Emiliano Trías, Luis Barbeito, Ignacio Anegón, María Cristina Cuturi, Pedro M. Moraes‐Vieira, Mercedes Segovia, Marcelo Hill,
Tópico(s)Inflammasome and immune disorders
ResumoSevere 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.
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