Poly(I:C) Enhances Mesenchymal Stem CellControl of Myeloid Cells and CorrectDysfunction in COVID-19. Souza-Moreira, L.et al.
Using a combination of ex vivo models (whole blood culture), we reveal that poly(I:C)-primed MSCs enhance the antiviral and modulatory ability of MSCs, leading to the recalibration of the dysregulated immune cellular response in COVID-19 patient whole blood samples. This study demonstrates that MSCs can be induced to upregulate antiviral protein expression while enhancing the ability to modulate patient immune cells, including direct evidence of MSCs and immune cells in the context of severe COVID-19. We establish a unique ex-vivo MSC co-culture system using whole blood from healthy donors and severe COVID-19 patients to examine the modulation of MSCs on acute inflammation, and severe COVID-19 immune responses. Deep profiling of the immune landscape using mass cytometry (CyTOF) reveals how viral mimic poly(I:C) enhanced MSCs’ influence on specific immune cell compositions, particularly on phenotypic and functional shifts on the myeloid-derived populations to the less inflammatory phenotypes. A SARS-CoV-2 pseudoviral system is utilized to demonstrate, for the first time, that poly(I:C)-priming enhances MSCs’ ability to block pseudoviral entry into lung epithelial cells.