TY  - JOUR
AU  - Rommel, Marcel G E
AU  - Walz, Lisa
AU  - Fotopoulou, Foteini
AU  - Kohlscheen, Saskia
AU  - Schenk, Franziska
AU  - Miskey, Csaba
AU  - Botezatu, Lacramioara
AU  - Krebs, Yvonne
AU  - Voelker, Iris M
AU  - Wittwer, Kevin
AU  - Holland-Letz, Tim
AU  - Ivics, Zoltán
AU  - von Messling, Veronika
AU  - Essers, Marieke A G
AU  - Milsom, Michael D
AU  - Pfaller, Christian K
AU  - Modlich, Ute
TI  - Influenza A virus infection instructs hematopoiesis to megakaryocyte-lineage output.
JO  - Cell reports
VL  - 41
IS  - 1
SN  - 2211-1247
CY  - [New York, NY]
PB  - Elsevier
M1  - DKFZ-2022-02338
SP  - 111447
PY  - 2022
AB  - 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.
KW  - CP: Immunology (Other)
KW  - CP: Microbiology (Other)
KW  - cytokines (Other)
KW  - emergency megakaryopoiesis (Other)
KW  - hematopoietic stem cell activation (Other)
KW  - inflammation (Other)
KW  - influenza (Other)
KW  - platelet activation (Other)
KW  - respiratory virus infection (Other)
KW  - vaccination (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36198277
DO  - DOI:10.1016/j.celrep.2022.111447
UR  - https://inrepo02.dkfz.de/record/181976
ER  -