G-CSF enhances neutrophil function with potential involvement of INHBA during Aspergillus fumigatus infection.

INTRODUCTION

Aspergillus fumigatus causes life-threatening infections in immunocompromised individuals. Neutrophils are essential for antifungal defence, but their function is often impaired in these patients. Granulocyte colony-stimulating factor (G-CSF) supports neutrophil survival and activation, yet systemic use can induce unwanted inflammation. The molecular mechanisms by which G-CSF enhances neutrophil function remain incompletely defined.

OBJECTIVES

To investigate whether ex vivo G-CSF-activated neutrophil transfer improves outcomes in invasive A. fumigatus infection and to explore the potential involvement of INHBA in regulating neutrophil dysfunction.

METHODS

Immunosuppressed mice were intranasally infected with A. fumigatus and subsequently received intravenous administration of G-CSF-activated neutrophils. Fungal burden, pulmonary inflammation, and cytokine expression were assessed. Transcriptomic and single-cell RNA sequencing analyses identified pathways regulated by G-CSF and INHBA. In vitro assays examined the impact of recombinant INHBA on neutrophil functions.

RESULTS

Transfer of G-CSF-activated neutrophils significantly improved survival, reduced fungal load, and decreased lung inflammation. G-CSF downregulated INHBA, while patient neutrophils displayed elevated INHBA expression. Functional studies showed INHBA suppressed neutrophil chemotaxis, phagocytosis, and NET formation.

CONCLUSION

G-CSF enhances neutrophil antifungal activity and is associated with modulation INHBA, suggesting a potential regulatory axis in neutrophil dysfunction during A. fumigatus infection. Ex vivo G-CSF-activated neutrophil transfer may represent a promising immunotherapeutic strategy for invasive aspergillosis.