M-CSF Directs Myeloid and NK Cell Differentiation to Protect from CMV After Hematopoietic Cell Transplantation

Overview

Journal EMBO Mol Med

Specialty Molecular Biology

Date 2023 Aug 28

PMID 37635627

Authors

Prashanth K Kandalla

Julien Subburayalu

Clement Cocita

Berengere de Laval

Elena Tomasello

Johanna Iacono

Jessica Nitsche

Maria M Canali

Wilfried Cathou

Gilles Bessou

Noushin Mossadegh-Keller

Caroline Huber

Guy Mouchiroud

Roland P Bourette

Marie-France Grasset

Martin Bornhauser

Sandrine Sarrazin

Marc Dalod

Michael H Sieweke

Affiliations

Soon will be listed here.

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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