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M-CSF directs myeloid and NK cell differentiation to protect from CMV after hematopoietic cell transplantation.

Kandalla, PK ; Subburayalu, J ; et al.
In: EMBO molecular medicine, Jg. 15 (2023-11-08), Heft 11, S. e17694
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Therapies reconstituting autologous antiviral immunocompetence may represent an important prophylaxis and treatment for immunosuppressed individuals. Following hematopoietic cell transplantation (HCT), patients are susceptible to Herpesviridae including cytomegalovirus (CMV). We show in a murine model of HCT that macrophage colony-stimulating factor (M-CSF) promoted rapid antiviral activity and protection from viremia caused by murine CMV. M-CSF given at transplantation stimulated sequential myeloid and natural killer (NK) cell differentiation culminating in increased NK cell numbers, production of granzyme B and interferon-γ. This depended upon M-CSF-induced myelopoiesis leading to IL15Rα-mediated presentation of IL-15 on monocytes, augmented by type I interferons from plasmacytoid dendritic cells. Demonstrating relevance to human HCT, M-CSF induced myelomonocytic IL15Rα expression and numbers of functional NK cells in G-CSF-mobilized hematopoietic stem and progenitor cells. Together, M-CSF-induced 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-CSF to rapidly reconstitute antiviral activity in immunocompromised individuals, which may provide a general paradigm to boost innate antiviral immunocompetence using host-directed therapies.

(© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Titel:
M-CSF directs myeloid and NK cell differentiation to protect from CMV after hematopoietic cell transplantation.
Autor/in / Beteiligte Person: Kandalla, PK ; Subburayalu, J ; Cocita, C ; de Laval B ; Tomasello, E ; Iacono, J ; Nitsche, J ; Canali, MM ; Cathou, W ; Bessou, G ; Mossadegh-Keller, N ; Huber, C ; Mouchiroud, G ; Bourette, RP ; Grasset, MF ; Bornhäuser, M ; Sarrazin, S ; Dalod, M ; Sieweke, MH
Link:
Zeitschrift: EMBO molecular medicine, Jg. 15 (2023-11-08), Heft 11, S. e17694
Veröffentlichung: 2024- : [London] : Nature Publishing Group ; <i>Original Publication</i>: Chichester, West Sussex : Wiley-Blackwell, 2023
Medientyp: academicJournal
ISSN: 1757-4684 (electronic)
DOI: 10.15252/emmm.202317694
Schlagwort:
  • Humans
  • Mice
  • Animals
  • Cytomegalovirus
  • Macrophage Colony-Stimulating Factor
  • Hematopoiesis
  • Antiviral Agents pharmacology
  • Antiviral Agents therapeutic use
  • Cell Differentiation
  • Hematopoietic Stem Cell Transplantation methods
  • Cytomegalovirus Infections prevention & control
Sonstiges:
  • Nachgewiesen in: MEDLINE
  • Sprachen: English
  • Publication Type: Journal Article; Research Support, Non-U.S. Gov't
  • Language: English
  • [EMBO Mol Med] 2023 Nov 08; Vol. 15 (11), pp. e17694. <i>Date of Electronic Publication: </i>2023 Aug 28.
  • MeSH Terms: Hematopoietic Stem Cell Transplantation* / methods ; Cytomegalovirus Infections* / prevention & control ; Humans ; Mice ; Animals ; Cytomegalovirus ; Macrophage Colony-Stimulating Factor ; Hematopoiesis ; Antiviral Agents / pharmacology ; Antiviral Agents / therapeutic use ; Cell Differentiation
  • Comments: Comment in: EMBO Mol Med. 2023 Nov 8;15(11):e18319. (PMID: 37697915)
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  • Contributed Indexing: Keywords: CMV (prophylaxis); HCT; M-CSF (CSF-1); NK cell; host-directed therapy
  • Substance Nomenclature: 81627-83-0 (Macrophage Colony-Stimulating Factor) ; 0 (Antiviral Agents)
  • Entry Date(s): Date Created: 20230828 Date Completed: 20231109 Latest Revision: 20231114
  • Update Code: 20231215
  • PubMed Central ID: PMC10630876

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