Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity
| Autor: | Falck-Jones, Sara, Vangeti, Sindhu, Yu, Meng, Falck-Jones, Ryan, Cagigi, Alberto, Badolati, Isabella, Österberg, Björn, Lautenbach, Maximilian Julius, Åhlberg, Eric, Lin, Ang, Lepzien, Rico, Szurgot, Inga, Lenart, Klara, Hellgren, Fredrika, Maecker, Holden, Sälde, Jörgen, Albert, Jan, Johansson, Niclas, Bell, Max, Loré, Karin, Färnert, Anna, Smed-Sörensen, Anna |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Aged 80 and over Male Arginase Interleukin-6 SARS-CoV-2 Myeloid-Derived Suppressor Cells T-Lymphocytes Respiratory System COVID-19 Middle Aged Severity of Illness Index Cohort Studies Interferon-gamma Leukocyte Count Young Adult Case-Control Studies Influenza Human Humans Female Pandemics Research Article Aged |
| Zdroj: | J Clin Invest |
| Popis: | The immunopathology of coronavirus disease 2019 (COVID-19) remains enigmatic, causing immunodysregulation and T cell lymphopenia. Monocytic myeloid-derived suppressor cells (M-MDSCs) are T cell suppressors that expand in inflammatory conditions, but their role in acute respiratory infections remains unclear. We studied the blood and airways of patients with COVID-19 across disease severities at multiple time points. M-MDSC frequencies were elevated in blood but not in nasopharyngeal or endotracheal aspirates of patients with COVID-19 compared with healthy controls. M-MDSCs isolated from patients with COVID-19 suppressed T cell proliferation and IFN-γ production partly via an arginase 1-dependent (Arg-1-dependent) mechanism. Furthermore, patients showed increased Arg-1 and IL-6 plasma levels. Patients with COVID-19 had fewer T cells and downregulated expression of the CD3ζ chain. Ordinal regression showed that early M-MDSC frequency predicted subsequent disease severity. In conclusion, M-MDSCs expanded in the blood of patients with COVID-19, suppressed T cells, and were strongly associated with disease severity, indicating a role for M-MDSCs in the dysregulated COVID-19 immune response. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|