%0 Journal Article
%A Rommel, Marcel G E
%A Walz, Lisa
%A Fotopoulou, Foteini
%A Kohlscheen, Saskia
%A Schenk, Franziska
%A Miskey, Csaba
%A Botezatu, Lacramioara
%A Krebs, Yvonne
%A Voelker, Iris M
%A Wittwer, Kevin
%A Holland-Letz, Tim
%A Ivics, Zoltán
%A von Messling, Veronika
%A Essers, Marieke A G
%A Milsom, Michael D
%A Pfaller, Christian K
%A Modlich, Ute
%T Influenza A virus infection instructs hematopoiesis to megakaryocyte-lineage output.
%J Cell reports
%V 41
%N 1
%@ 2211-1247
%C [New York, NY]
%I Elsevier
%M DKFZ-2022-02338
%P 111447
%D 2022
%X 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.
%K CP: Immunology (Other)
%K CP: Microbiology (Other)
%K cytokines (Other)
%K emergency megakaryopoiesis (Other)
%K hematopoietic stem cell activation (Other)
%K inflammation (Other)
%K influenza (Other)
%K platelet activation (Other)
%K respiratory virus infection (Other)
%K vaccination (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36198277
%R 10.1016/j.celrep.2022.111447
%U https://inrepo02.dkfz.de/record/181976