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Following hematopoietic cell transplantation (HCT), patients are susceptible to\n                    <jats:italic>Herpesviridae<\/jats:italic>\n                    including cytomegalovirus (CMV). We show in a murine model of HCT that macrophage colony\u2010stimulating factor (M\u2010CSF) promoted rapid antiviral activity and protection from viremia caused by murine CMV. M\u2010CSF given at transplantation stimulated sequential myeloid and natural killer (NK) cell differentiation culminating in increased NK cell numbers, production of granzyme B and interferon\u2010\u03b3. This depended upon M\u2010CSF\u2010induced myelopoiesis leading to IL15R\u03b1\u2010mediated presentation of IL\u201015 on monocytes, augmented by type I interferons from plasmacytoid dendritic cells. Demonstrating relevance to human HCT, M\u2010CSF induced myelomonocytic IL15R\u03b1 expression and numbers of functional NK cells in G\u2010CSF\u2010mobilized hematopoietic stem and progenitor cells. Together, M\u2010CSF\u2010induced myelopoiesis triggered an integrated differentiation of myeloid and NK cells to protect HCT recipients from CMV. Thus, our results identify a rationale for the therapeutic use of M\u2010CSF to rapidly reconstitute antiviral activity in immunocompromised individuals, which may provide a general paradigm to boost innate antiviral immunocompetence using host\u2010directed therapies.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202317694","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T03:28:44Z","timestamp":1693193324000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["M\u2010CSF directs myeloid and NK cell differentiation to protect from CMV after hematopoietic cell transplantation"],"prefix":"10.1038","volume":"15","author":[{"given":"Prashanth K","family":"Kandalla","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9243-0558","authenticated-orcid":false,"given":"Julien","family":"Subburayalu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cl\u00e9ment","family":"Cocita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B\u00e9reng\u00e8re","family":"de Laval","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Tomasello","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna","family":"Iacono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7267-7857","authenticated-orcid":false,"given":"Jessica","family":"Nitsche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5787-7909","authenticated-orcid":false,"given":"Maria M","family":"Canali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilfried","family":"Cathou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilles","family":"Bessou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7088-3676","authenticated-orcid":false,"given":"Noushin","family":"Mossadegh\u2010Keller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Huber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7823-7353","authenticated-orcid":false,"given":"Guy","family":"Mouchiroud","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2074-4878","authenticated-orcid":false,"given":"Roland P","family":"Bourette","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie\u2010France","family":"Grasset","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5916-3029","authenticated-orcid":false,"given":"Martin","family":"Bornh\u00e4user","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6435-0913","authenticated-orcid":false,"given":"Sandrine","family":"Sarrazin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6436-7966","authenticated-orcid":false,"given":"Marc","family":"Dalod","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3228-9537","authenticated-orcid":false,"given":"Michael H","family":"Sieweke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,8,28]]},"reference":[{"key":"BFEMMM202317694_CR1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.2174\/187152611797636640","volume":"11","author":"A Ahmed","year":"2011","unstructured":"Ahmed A (2011) Antiviral treatment of cytomegalovirus infection. 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