Publication date: 13 June 2017
Source:Cell Reports, Volume 19, Issue 11
Author(s): Christoph Hirche, Theresa Frenz, Simon F. Haas, Marius Döring, Katharina Borst, Pia-K. Tegtmeyer, Ilija Brizic, Stefan Jordan, Kirsten Keyser, Chintan Chhatbar, Eline Pronk, Shuiping Lin, Martin Messerle, Stipan Jonjic, Christine S. Falk, Andreas Trumpp, Marieke A.G. Essers, Ulrich Kalinke
Quiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis virus (VSV) and murine cytomegalovirus (MCMV) infection induce LT-HSC activation that substantially differs from the effects triggered upon injection of synthetic IFN-I-inducing agents. In both infections, inflammatory responses had to exceed local thresholds within the bone marrow to confer LT-HSC cell cycle entry, and IFN-I receptor triggering was not critical for this activation. After resolution of acute MCMV infection, LT-HSCs returned to phenotypic quiescence. However, non-acute MCMV infection induced a sustained inflammatory milieu within the bone marrow that was associated with long-lasting impairment of LT-HSC function. In conclusion, our results show that systemic virus infections fundamentally affect LT-HSCs and that also non-acute inflammatory stimuli in bone marrow donors can affect the reconstitution potential of bone marrow transplants.
Graphical abstract
Teaser
Long-term hematopoietic stem cells (LT-HSCs) are activated by recombinant type I interferon (IFN-I). Hirche et al. report here that acute systemic virus infections activate LT-HSCs independently of IFN-I receptor signaling. Non-acute infection of bone marrow donors impacts LT-HSC function, but not phenotype, potentially explaining clinical complications following bone marrow transplantations.http://ift.tt/2t2xJNa
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου