Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections.

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.

• Authors: Alan Bénard, Anne Jacobsen, Maximilian Brunner, Christian Krautz, Bettina Klösch, Izabela Swierzy, Elisabeth Naschberger, Malgorzata J Podolska, Dina Kouhestani, Paul David, Torsten Birkholz, Ixchel Castellanos, Denis Trufa, Horia Sirbu, Marcel Vetter, Andreas E Kremer, Kai Hildner, Andreas Hecker, Fabian Edinger, Matthias Tenbusch, Petra Mühl-Zürbes, Alexander Steinkasserer, Enrico Richter, Hendrik Streeck, Marc M Berger, Thorsten Brenner, Markus A Weigand, Filip K Swirski, Georg Schett, Robert Grützmann, Georg F Weber
• Journal: Nature communications (Nat Commun) Vol. 12 Issue 1 Pg. 1112 (02 18 2021) ISSN: 2041-1723 [Electronic] England
• PMID: 33602937 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't)

Chemical References

• Chemokine CXCL12
• IL3 protein, human
• Interleukin-3
• Interferons

Topics

• Animals
• COVID-19 (diagnosis, mortality)
• Chemokine CXCL12 (immunology)
• Dendritic Cells (cytology)
• Disease Models, Animal
• Female
• Germany
• Humans
• Immunity, Innate
• Interferons (blood)
• Interleukin-3 (blood)
• Lung (immunology, virology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Prospective Studies
• Severity of Illness Index
• T-Lymphocytes (cytology)
• Viral Load