# Adjunctive GM-CSF therapy enhances host defense against systemic Candida auris infection in immunosuppressed mice

## TL;DR

This study shows that GM-CSF therapy improves survival and reduces fungal spread in mice infected with drug-resistant Candida auris.

## Contribution

The novel finding is that GM-CSF, alone or with micafungin, enhances host immunity against C. auris in immunosuppressed mice.

## Key findings

- GM-CSF monotherapy significantly improved survival and reduced fungal burden in multiple organs.
- GM-CSF increased macrophage and neutrophil populations and enhanced their antifungal functions.
- Combination therapy with GM-CSF and micafungin did not significantly improve outcomes beyond GM-CSF alone.

## Abstract

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.

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.

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.

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