Journal Article

DKFZ-2022-02338

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Influenza A virus infection instructs hematopoiesis to megakaryocyte-lineage output.

Rommel, M. G. E.Extern* ; Walz, L. ; Fotopoulou, F.DKFZ* ; Kohlscheen, S. ; Schenk, F. ; Miskey, C. ; Botezatu, L. ; Krebs, Y. ; Voelker, I. M. ; Wittwer, K. ; Holland-Letz, T.DKFZ* ; Ivics, Z. ; von Messling, V. ; Essers, M. A. G.DKFZ* ; Milsom, M. D.DKFZ* ; Pfaller, C. K. ; Modlich, U.

2022
Elsevier [New York, NY]

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Please use a persistent id in citations: doi:10.1016/j.celrep.2022.111447

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.

Keyword(s): CP: Immunology ; CP: Microbiology ; cytokines ; emergency megakaryopoiesis ; hematopoietic stem cell activation ; inflammation ; influenza ; platelet activation ; respiratory virus infection ; vaccination

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Contributing Institute(s):

1. A012 Experimentelle Hämatologie (A012)
2. C060 Biostatistik (C060)
3. A011 Stressinduzierte Aktivierung von Hämatopeotischen Stammzellen (A011)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2022

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