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

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  • Alan Bénard

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Anne Jacobsen

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Maximilian Brunner

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Christian Krautz

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Bettina Klösch

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Izabela Swierzy

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Elisabeth Naschberger

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Malgorzata J. Podolska

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Dina Kouhestani

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Paul David

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Torsten Birkholz

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Ixchel Castellanos

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Denis Trufa

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Horia Sirbu

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Marcel Vetter

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Andreas E. Kremer

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Kai Hildner

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Andreas Hecker

    (University Hospital)

  • Fabian Edinger

    (University Hospital)

  • Matthias Tenbusch

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Petra Mühl-Zürbes

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Alexander Steinkasserer

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Enrico Richter

    (University Hospital)

  • Hendrik Streeck

    (University Hospital)

  • Marc M. Berger

    (University Hospital Essen, University Duisburg-Essen)

  • Thorsten Brenner

    (University Hospital Essen, University Duisburg-Essen)

  • Markus A. Weigand

    (Heidelberg University Hospital)

  • Filip K. Swirski

    (Massachusetts General Hospital and Harvard Medical School)

  • Georg Schett

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Robert Grützmann

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

  • Georg F. Weber

    (Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen)

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.

Suggested Citation

  • Alan Bénard & Anne Jacobsen & Maximilian Brunner & Christian Krautz & Bettina Klösch & Izabela Swierzy & Elisabeth Naschberger & Malgorzata J. Podolska & Dina Kouhestani & Paul David & Torsten Birkhol, 2021. "Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections," Nature Communications, Nature, vol. 12(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21310-4
    DOI: 10.1038/s41467-021-21310-4
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    Cited by:

    1. John TCHEN & Quentin SIMON & Léa CHAPART & Morgane K. THAMINY & Shamila VIBHUSHAN & Loredana SAVEANU & Yasmine LAMRI & Fanny SAIDOUNE & Emeline PACREAU & Christophe PELLEFIGUES & Julie BEX-COUDRAT & H, 2024. "PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Manon Venet & Margarida Sa Ribeiro & Elodie Décembre & Alicia Bellomo & Garima Joshi & Célia Nuovo & Marine Villard & David Cluet & Magali Perret & Rémi Pescamona & Helena Paidassi & Thierry Walzer & , 2023. "Severe COVID-19 patients have impaired plasmacytoid dendritic cell-mediated control of SARS-CoV-2," Nature Communications, Nature, vol. 14(1), pages 1-21, December.

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