1. Influenza A virus infection instructs hematopoiesis to megakaryocyte-lineage output.
- Author
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Rommel MGE, Walz L, Fotopoulou F, Kohlscheen S, Schenk F, Miskey C, Botezatu L, Krebs Y, Voelker IM, Wittwer K, Holland-Letz T, Ivics Z, von Messling V, Essers MAG, Milsom MD, Pfaller CK, and Modlich U
- Subjects
- Animals, Antiviral Agents metabolism, Cytokines metabolism, Endothelial Protein C Receptor metabolism, Hematopoiesis, Humans, Megakaryocytes metabolism, Mice, Receptors, Interleukin-1 metabolism, Thrombopoietin metabolism, Influenza A virus, Influenza, Human metabolism
- Abstract
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., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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