Functional monocytic myeloid-derived suppressor cells increase in blood but not airways and predict COVID-19 severity
Journal of Clinical Investigation, 2021
Falck-Jones S., Vangeti S., Yu M., Falck-Jones R., Cagigi A., Badolati I., Österberg B., Lautenbach M., Åhlberg E., Lin A., Lepzien R., Szurgot I., Lenart K., Hellgren F., Maecker H., Sälde J., Albert J., Johansson N., Bell M., Loré K., Färnert A., Smed-Sörensen A.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Infectious Diseases | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
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.