Myeloid Cells Restrict MCMV and Drive Stress-Induced Extramedullary Hematopoiesis through STAT1.
Cytomegalovirus (CMV) has a high prevalence worldwide, is often fatal for immunocompromised patients, and causes bone marrow suppression. Deficiency of 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 myeloid cell activity for the defense against murine CMV (MCMV). We show that myeloid STAT1 limits MCMV burden and infection-associated pathology in the spleen but does not affect ultimate clearance of infection. Unexpectedly, we found an essential role of myeloid STAT1 in the induction of extramedullary hematopoiesis (EMH). The EMH-promoting function of STAT1 was not restricted to MCMV infection but was also observed during CpG oligodeoxynucleotide-induced sterile inflammation. Collectively, we provide genetic evidence that signaling through STAT1 in myeloid cells is required to restrict MCMV at early time points post-infection and to induce compensatory hematopoiesis in the spleen.
['Gawish|Riem|R|', 'Bulat|Tanja|T|', 'Biaggio|Mario|M|', 'Lassnig|Caroline|C|', 'Bago-Horvath|Zsuzsanna|Z|', 'Macho-Maschler|Sabine|S|', 'Poelzl|Andrea|A|', 'Simonović|Natalija|N|', 'Prchal-Murphy|Michaela|M|', 'Rom|Rita|R|', 'Amenitsch|Lena|L|', 'Ferrarese|Luca|L|', 'Kornhoff|Juliana|J|', 'Lederer|Therese|T|', 'Svinka|Jasmin|J|', 'Eferl|Robert|R|', 'Bosmann|Markus|M|', 'Kalinke|Ulrich|U|', 'Stoiber|Dagmar|D|', 'Sexl|Veronika|V|', 'Krmpotić|Astrid|A|', 'Jonjić|Stipan|S|', 'Müller|Mathias|M|', 'Strobl|Birgit|B|']
D000818:Animals D002478:Cells, Cultured D005260:Female D017353:Gene Deletion D006411:Hematopoiesis, Extramedullary D006566:Herpesviridae Infections D007694:Killer Cells, Natural D008297:Male D008810:Mice, Inbred C57BL D018146:Muromegalovirus D022423:Myeloid Cells D053633:Receptor, Interferon alpha-beta D017471:Receptors, Interferon D018123:Receptors, Interleukin D050794:STAT1 Transcription Factor D013154:Spleen D013312:Stress, Physiological D014779:Virus Replication
signal transducer and activator of transcription Herpesviridae IFN-I receptor IFN-II receptor IL-27 receptor TLR9 agonist monocytes