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

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Maite Duhalde Vega
Mauricio Bertullo
Ana Paula Arévalo
Martina Crispo
Germán Galliussi
David Charbonnier
Valentina Varela
Pablo Oppezzo
Emiliano Trias
Luis Barbeito

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.
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Origin : Publication funded by an institution

Dates and versions

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

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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⟩
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