Disharmonic Inflammatory Signatures in COVID-19: Augmented Neutrophils’ but Impaired Monocytes’ and Dendritic Cells’ Responsiveness
Zuzana Parackova,
Irena Zentsova,
Marketa Bloomfield,
Petra Vrabcova,
Jitka Smetanova,
Adam Klocperk,
Grigorij Mesežnikov,
Luis Fernando Casas Mendez,
Tomas Vymazal,
Anna Sediva
Affiliations
Zuzana Parackova
Department of Immunology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital in Motol, 15006 Prague, Czech Republic
Irena Zentsova
Department of Immunology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital in Motol, 15006 Prague, Czech Republic
Marketa Bloomfield
Department of Immunology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital in Motol, 15006 Prague, Czech Republic
Petra Vrabcova
Department of Immunology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital in Motol, 15006 Prague, Czech Republic
Jitka Smetanova
Department of Immunology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital in Motol, 15006 Prague, Czech Republic
Adam Klocperk
Department of Immunology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital in Motol, 15006 Prague, Czech Republic
Grigorij Mesežnikov
Department of Infectious Diseases, University Hospital in Motol, 15006 Prague, Czech Republic
Luis Fernando Casas Mendez
Department of Pneumology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital in Motol, 15006 Prague, Czech Republic
Tomas Vymazal
Department of Anesthesiology and Intensive Care Medicine, 2nd Faculty of Medicine, Charles University in Prague and University Hospital in Motol, 15006 Prague, Czech Republic
Anna Sediva
Department of Immunology, 2nd Faculty of Medicine, Charles University in Prague and University Hospital in Motol, 15006 Prague, Czech Republic
COVID-19, caused by SARS-CoV-2 virus, emerged as a pandemic disease posing a severe threat to global health. To date, sporadic studies have demonstrated that innate immune mechanisms, specifically neutrophilia, NETosis, and neutrophil-associated cytokine responses, are involved in COVID-19 pathogenesis; however, our understanding of the exact nature of this aspect of host–pathogen interaction is limited. Here, we present a detailed dissection of the features and functional profiles of neutrophils, dendritic cells, and monocytes in COVID-19. We portray the crucial role of neutrophils as drivers of hyperinflammation associated with COVID-19 disease via the shift towards their immature forms, enhanced degranulation, cytokine production, and augmented interferon responses. We demonstrate the impaired functionality of COVID-19 dendritic cells and monocytes, particularly their low expression of maturation markers, increased PD-L1 levels, and their inability to upregulate phenotype upon stimulation. In summary, our work highlights important data that prompt further research, as therapeutic targeting of neutrophils and their associated products may hold the potential to reduce the severity of COVID-19.