# Absence of neutrophils impairs the host defense in murine footpad model of chromoblastomycosis

## TL;DR

Neutrophils are crucial for fighting a chronic fungal infection called chromoblastomycosis, as their absence worsens infection outcomes and delays recovery.

## Contribution

The study reveals that neutrophils inhibit fungal morphological transitions and promote fungal clearance in chromoblastomycosis.

## Key findings

- Neutrophil depletion in mice led to impaired fungal clearance and prolonged inflammation.
- Neutrophils inhibit the morphological transition of F. monophora from conidia to hyphae and sclerotic-like cells.
- Neutrophil extracellular traps (NETs) formation is associated with F. monophora morphology in vitro.

## Abstract

Chromoblastomycosis (CBM), a chronic subcutaneous infection caused by black fungi such as Fonsecaea monophora (F. monophora), is characterized by a low cure rate, high recurrence rate, and prolonged treatment duration. Neutrophils, one of the most important innate immune cells, play complex roles in the prevention of fungal infections. This study investigated the function of neutrophils in host defense against F. monophora using a neutrophil-depleted mouse model and in vitro co-culture conditions. Fungal burden, histopathological changes, and cytokine profiles were compared between neutrophil-depleted mice and isotype control mice. Our findings demonstrated that neutrophil depletion in mice led to impaired fungal clearance, prolonged inflammation in F. monophora infected footpad tissues, highlighting the critical role of neutrophils in controlling F. monophora infection. Histopathological analysis revealed extensive inflammatory cell infiltration, especially macrophages, accompanied by elevated levels of pro-inflammatory cytokines such as IL-1β, CCL3, IL-6, and TNF-α. Besides, we observed that neutrophils play a key role in inhibiting the morphological transition of F. monophora from conidia to hyphae and sclerotic-like cells. Notably, the F. monophora morphology was also associated with the formation of neutrophil extracellular traps (NETs) in in vitro experiment. These findings underscore the importance of neutrophil-mediate immune responses in early fungal clearance and their ability to influence F.monophora morphological transition. The study provides novel insights into the immune mechanisms underlying CBM and highlights the potential therapeutic implications of targeting neutrophil-mediated responses in CBM infections.

Chromoblastomycosis (CBM) is a chronic subcutaneous infection caused by black fungi such as Fonsecaea monophora (F. monophora), known for its low cure rate, high recurrence, and prolonged treatment. Neutrophils, key players in innate immunity, play a crucial role in defending against fungal infections. This study investigated the function of neutrophils in host defense against F. monophora using a neutrophil-depleted mouse model and in vitro experiments. Results showed that neutrophil depletion impaired fungal clearance and prolonged inflammation in infected tissues, emphasizing their critical role in controlling F. monophora infection. Histopathological analysis revealed extensive inflammatory cell infiltration, particularly macrophages. Neutrophils also inhibited the fungal transition from conidia to hyphae and sclerotic-like cells. Notably, the F. monophora morphology was also associated with the formation of neutrophil extracellular traps (NETs) in vitro experiments. These findings reveal the importance of neutrophils in early fungal clearance and morphology regulation, offering insights into immune mechanisms and potential therapeutic strategies targeting neutrophil-mediated responses for CBM.