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Article Dans Une Revue EMBO Molecular Medicine Année : 2023

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

Prashanth Kandalla
  • Fonction : Auteur
Julien Subburayalu
Clément Cocita
  • Fonction : Auteur
Bérengère de Laval
  • Fonction : Auteur
Elena Tomasello
  • Fonction : Auteur
Johanna Iacono
  • Fonction : Auteur
Jessica Nitsche
Maria Canali
Wilfried Cathou
  • Fonction : Auteur
Gilles Bessou
  • Fonction : Auteur
Noushin Mossadegh-Keller
Caroline Huber
  • Fonction : Auteur
Guy Mouchiroud
Roland Bourette
Marie‐france Grasset
  • Fonction : Auteur
Martin Bornhäuser
Sandrine Sarrazin
Marc Dalod
Michael Sieweke

Résumé

Abstract 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.
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Dates et versions

hal-04275303 , version 1 (12-11-2023)

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Prashanth Kandalla, Julien Subburayalu, Clément Cocita, Bérengère de Laval, Elena Tomasello, et al.. M‐CSF directs myeloid and NK cell differentiation to protect from CMV after hematopoietic cell transplantation. EMBO Molecular Medicine, 2023, 15 (11), ⟨10.15252/emmm.202317694⟩. ⟨hal-04275303⟩
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