1. Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections.
- Author
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Bénard A, Jacobsen A, Brunner M, Krautz C, Klösch B, Swierzy I, Naschberger E, Podolska MJ, Kouhestani D, David P, Birkholz T, Castellanos I, Trufa D, Sirbu H, Vetter M, Kremer AE, Hildner K, Hecker A, Edinger F, Tenbusch M, Mühl-Zürbes P, Steinkasserer A, Richter E, Streeck H, Berger MM, Brenner T, Weigand MA, Swirski FK, Schett G, Grützmann R, and Weber GF
- Subjects
- Animals, COVID-19 mortality, Chemokine CXCL12 immunology, Dendritic Cells cytology, Disease Models, Animal, Female, Germany, Humans, Immunity, Innate, Interferons blood, Lung immunology, Lung virology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Prospective Studies, Severity of Illness Index, T-Lymphocytes cytology, Viral Load, COVID-19 diagnosis, Interleukin-3 blood
- Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide health threat. In a prospective multicentric study, we identify IL-3 as an independent prognostic marker for the outcome during SARS-CoV-2 infections. Specifically, low plasma IL-3 levels is associated with increased severity, viral load, and mortality during SARS-CoV-2 infections. Patients with severe COVID-19 exhibit also reduced circulating plasmacytoid dendritic cells (pDCs) and low plasma IFNα and IFNλ levels when compared to non-severe COVID-19 patients. In a mouse model of pulmonary HSV-1 infection, treatment with recombinant IL-3 reduces viral load and mortality. Mechanistically, IL-3 increases innate antiviral immunity by promoting the recruitment of circulating pDCs into the airways by stimulating CXCL12 secretion from pulmonary CD123
+ epithelial cells, both, in mice and in COVID-19 negative patients exhibiting pulmonary diseases. This study identifies IL-3 as a predictive disease marker for SARS-CoV-2 infections and as a potential therapeutic target for pulmunory viral infections.- Published
- 2021
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