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Nat Commun
. 2021 Feb 18;12(1):1112.
doi: 10.1038/s41467-021-21310-4.
Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections
Alan B?nard 1 , Anne Jacobsen 2 , Maximilian Brunner 2 , Christian Krautz 2 , Bettina Kl?sch 2 , Izabela Swierzy 2 , Elisabeth Naschberger 2 , Malgorzata J Podolska 2 , Dina Kouhestani 2 , Paul David 2 , Torsten Birkholz 3 , Ixchel Castellanos 3 , Denis Trufa 4 , Horia Sirbu 4 , Marcel Vetter 5 , Andreas E Kremer 5 , Kai Hildner 5 , Andreas Hecker 6 , Fabian Edinger 6 , Matthias Tenbusch 7 , Petra M?hl-Z?rbes 8 , Alexander Steinkasserer 8 , Enrico Richter 9 , Hendrik Streeck 9 , Marc M Berger 10 , Thorsten Brenner 10 , Markus A Weigand 11 , Filip K Swirski 12 , Georg Schett 13 , Robert Gr?tzmann 2 , Georg F Weber 14
Affiliations
- PMID: 33602937
- DOI: 10.1038/s41467-021-21310-4
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.