Cytomegalovirus (CMV) has a high prevalence worldwide, is often fatal for immunocompromised patients and causes bone marrow suppression. Deficiency for signal transducer and activator of transcription 1 (STAT1) results in severely impaired antiviral immunity. We have used cell-type restricted deletion of Stat1 to determine the importance of macrophage activity for the defence against murine CMV (MCMV). We show that macrophage STAT1 limits MCMV burden and infection-associated pathology in the spleen, but does not impact on ultimate clearance of infection. Surprisingly, we found an essential role of macrophage STAT1 in the induction of extramedullary hematopoiesis (EMH). The EMH-promoting function of STAT1 was not only observed after MCMV infection but also during CpG oligodeoxynucleotide-induced sterile inflammation. Collectively, we provide the first genetic evidence that signalling through STAT1 in macrophages is required to restrict MCMV at early time points post infection and to induce compensatory hematopoiesis in the spleen.
Gawish, Riem and Biaggio, Mario and Lassnig, Caroline and Bago-Horvath, Zsuzsanna and Macho-Maschler, Sabine and Rom, Rita and Amenitsch, Lena and Ferrarese, Luca and Kornhoff, Juliana and Lederer, Therese and Krmpotić, Astrid and Jonjić, Stipan and Müller, Mathias and Strobl, Birgit, Macrophages Restrict MCMV and Drive Stress-Induced Extramedullary Hematopoiesis Through STAT1 (2018). Available at SSRN: https://ssrn.com/abstract=3155784 or http://dx.doi.org/10.2139/ssrn.3155784
This version of the paper has not been formally peer reviewed.
Download This Paper