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PreprintCC BYbioRxiv

GM-CSF signaling on monocytes and monocyte-derived dendritic cells is required for effective pulmonary immunity to Aspergillus fumigatus

  1. 1Memorial Sloan Kettering Cancer Center

Abstract

Aspergillus fumigatus is the most common cause of invasive aspergillosis (IA), an opportunistic pulmonary infection of immunocompromised patients that can be fatal, despite treatment with modern antifungal drugs. During infection, myeloid cells, such as neutrophils, monocytes, and monocyte-derived dendritic cells (Mo-DCs) are recruited to the lung and are critical for phagocytosing and killing A. fumigatus spores. Recent evidence has shown that intracellular crosstalk between these professional immune cells and other resident pulmonary cell types is required for an effective immune response to A. fumigatus, and that signaling via the cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) is part of this intracellular communication. In this study, we sought to determine a role for GM-CSF signaling on monocytes and their progeny. We harnessed a mouse model of deletion of GM-CSF receptor {beta} chain (encoded by Csf2rb) in CCR2-expressing cells. Using this model, we found that GM-CSF signaling is required on CCR2+ cells for killing of A. fumigatus and for host survival. This observation expands the importance of GM-CSF in host defense during A. fumigatus pulmonary infection and extends its role in pathways of intracellular crosstalk that mediate effective pulmonary antifungal immunity.

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BibTeX
@misc{mills2026gmcsf,
  title = {{GM-CSF signaling on monocytes and monocyte-derived dendritic cells is required for effective pulmonary immunity to Aspergillus fumigatus}},
  author = {K. A. M. Mills and B. Becher and T. M. Hohl},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.22.753578},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.22.753578v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - GM-CSF signaling on monocytes and monocyte-derived dendritic cells is required for effective pulmonary immunity to Aspergillus fumigatus
AU  - K. A. M. Mills
AU  - B. Becher
AU  - T. M. Hohl
PY  - 2026
DA  - 2026/09/22
PB  - bioRxiv
DO  - 10.64898/2026.09.22.753578
UR  - https://www.biorxiv.org/content/10.64898/2026.09.22.753578v1
AB  - Aspergillus fumigatus is the most common cause of invasive aspergillosis (IA), an opportunistic pulmonary infection of immunocompromised patients that can be fatal, despite treatment with modern antifungal drugs. During infection, myeloid cells, such as neutrophils, monocytes, and monocyte-derived dendritic cells (Mo-DCs) are recruited to the lung and are critical for phagocytosing and killing A. fumigatus spores. Recent evidence has shown that intracellular crosstalk between these professional immune cells and other resident pulmonary cell types is required for an effective immune response to A. fumigatus, and that signaling via the cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) is part of this intracellular communication. In this study, we sought to determine a role for GM-CSF signaling on monocytes and their progeny. We harnessed a mouse model of deletion of GM-CSF receptor {beta} chain (encoded by Csf2rb) in CCR2-expressing cells. Using this model, we found that GM-CSF signaling is required on CCR2+ cells for killing of A. fumigatus and for host survival. This observation expands the importance of GM-CSF in host defense during A. fumigatus pulmonary infection and extends its role in pathways of intracellular crosstalk that mediate effective pulmonary antifungal immunity.
ER  -