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Influenza A virus infection instructs hematopoiesis to megakaryocyte-lineage output

Respiratory tract infections are among the deadliest communicable diseases worldwide. Severe cases of viral lung infections are often associated with a cytokine storm and alternating platelet numbers. We report that hematopoietic stem and progenitor cells (HSPCs) sense a non-systemic influenza A vir...

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Main Authors: Rommel, Marcel G. E. (Author) , Walz, Lisa (Author) , Fotopoulou, Foteini (Author) , Kohlscheen, Saskia (Author) , Schenk, Franziska (Author) , Miskey, Csaba (Author) , Botezatu, Lacramioara (Author) , Krebs, Yvonne (Author) , Voelker, Iris M. (Author) , Wittwer, Kevin (Author) , Holland-Letz, Tim (Author) , Ivics, Zoltán (Author) , von Messling, Veronika (Author) , Essers, Marieke A. G. (Author) , Milsom, Michael (Author) , Pfaller, Christian K. (Author) , Modlich, Ute (Author)
Format: Article (Journal)
Language:English
Published: October 4, 2022
In: Cell reports
Year: 2022, Volume: 41, Issue: 1, Pages: 1-18
ISSN:2211-1247
DOI:10.1016/j.celrep.2022.111447
Online Access:Resolving-System, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2022.111447
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124722012888
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Author Notes:Marcel G.E. Rommel, Lisa Walz, Foteini Fotopoulou, Saskia Kohlscheen, Franziska Schenk, Csaba Miskey, Lacramioara Botezatu, Yvonne Krebs, Iris M. Voelker, Kevin Wittwer, Tim Holland-Letz, Zoltán Ivics, Veronika von Messling, Marieke A.G. Essers, Michael D. Milsom, Christian K. Pfaller, and Ute Modlich
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Summary:Respiratory tract infections are among the deadliest communicable diseases worldwide. Severe cases of viral lung infections are often associated with a cytokine storm and alternating platelet numbers. We report that hematopoietic stem and progenitor cells (HSPCs) sense a non-systemic influenza A virus (IAV) infection via inflammatory cytokines. Irrespective of antiviral treatment or vaccination, at a certain threshold of IAV titer in the lung, CD41-positive hematopoietic stem cells (HSCs) enter the cell cycle while endothelial protein C receptor-positive CD41-negative HSCs remain quiescent. Active CD41-positive HSCs represent the source of megakaryocytes, while their multi-lineage reconstitution potential is reduced. This emergency megakaryopoiesis is thrombopoietin independent and attenuated in IAV-infected interleukin-1 receptor-deficient mice. Newly produced platelets during IAV infection are immature and hyper-reactive. After viral clearance, HSC quiescence is re-established. Our study reveals that non-systemic viral respiratory infection has an acute impact on HSCs via inflammatory cytokines to counteract IAV-induced thrombocytopenia.
Item Description:Gesehen am 26.10.2022
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2022.111447

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