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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

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.

Details

Original languageEnglish
Article numbere17694
JournalEMBO molecular medicine
Volume15
Issue number11
Publication statusPublished - 8 Nov 2023
Peer-reviewedYes

External IDs

PubMed 37635627

Keywords

Research priority areas of TU Dresden

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • CMV (prophylaxis), HCT, M-CSF (CSF-1), NK cell, host-directed therapy, Cytomegalovirus, Humans, Macrophage Colony-Stimulating Factor, Animals, Hematopoietic Stem Cell Transplantation/methods, Hematopoiesis, Antiviral Agents/pharmacology, Mice, Cell Differentiation, Cytomegalovirus Infections/prevention & control