Influenza A virus infection instructs hematopoiesis to megakaryocyte-lineage output
M 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 Essers, Michael D. Milsom, Christian K. Pfaller, Ute Modlich
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.