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Terapia adyuvante con GM-CSF mejora la defensa del huésped contra la infección sistémica por Candida auris en ratones

Eliciane Cevolani Mattos¹, Kaustav Das Gupta¹, Derek Quintanilla¹

¹Division of Infectious Disease, The Lundquist Institute for Biomedical Innovation at Harbor-University of California, Los Angeles Medical Center, Torrance, CA, United States.

Frontiers in immunology

|February 4, 2026

Abstracto

Introduction:

Candida auris is an emerging, multidrug-resistant fungal pathogen associated with high mortality in immunocompromised individuals. Resistance to current antifungal drugs emphasizes the need for new therapeutic approaches. We investigated granulocyte-macrophage colony-stimulating factor (GM-CSF) as a standalone immunotherapy and in combination with a sub-therapeutic dose of micafungin in an immunosuppressed mouse model of systemic C. auris infection.

Methods:

Immunosuppressed ICR CD-1 mice (4-6 weeks old) were infected with C. auris and treated daily via intraperitoneal injection with PBS (placebo), murine GM-CSF (0.2 or 2 μg), micafungin, or both. Treatments began 24 h post-infection and continued through day 4 (GM-CSF) or day 7 (micafungin). Survival, tissue fungal burden, histopathology, and immune cell frequencies in spleen and kidneys were assessed. GM-CSF effects on neutrophil and macrophage antifungal functions were evaluated in ex vivo assays.

Results:

GM-CSF monotherapy significantly improved survival (30-32% vs. 0% in controls), extended median survival time, and reduced fungal burden in the kidney, heart, and brain. Although the combination therapy yielded the highest survival rate, it did not differ significantly from GM-CSF alone. Histopathological examination confirmed decreased fungal load and tissue damage in GM-CSF-treated mice. Additionally, GM-CSF augmented macrophage and neutrophil populations in spleen and kidney, enhanced fungal uptake and killing via reactive oxygen species and neutrophil extracellular traps.

Discussion:

GM-CSF augments antifungal immunity and represents a promising adjunctive immunotherapy against MDR C. auris infection.

Palabras clave:

Candida auris GM-CSF Inmunosupresión inmunidad antifúngica inmunoterapia macrófago neutrófilos modelo de infección sistémica murina

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