Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus fumigatus

Area of Science:

• Mycology
• Immunology
• Infectious Diseases

Background:

• Invasive aspergillosis (IA) is a severe opportunistic infection caused by Aspergillus fumigatus.
• IA affects immunocompromised patients, leading to high mortality.
• Current research on neutrophil-hypha interactions in IA is limited by control over temporal and spatial dynamics.

Purpose of the Study:

• To develop a novel method for studying neutrophil-hypha interactions at single-cell resolution over time.
• To elucidate the fungal response to neutrophil encounters during invasive aspergillosis.

Main Methods:

• A new in vitro approach enabling real-time, single-cell observation of neutrophil-hypha interactions.
• Analysis of fungal branching patterns and their dependence on neutrophil activity.

Main Results:

• Aspergillus fumigatus hyphae exhibit de novo tip formation, creating branches to evade neutrophil interaction points and continue invasive growth.
• This evasive branching is triggered independently of neutrophil NADPH oxidase activity and neutrophil extracellular trap (NET) formation.
• The mechanism can be mimicked by iron chelation or by physically impeding hyphal tip extension.
• The outcome of branching depends on neutrophil availability: abundant neutrophils lead to hyphal destruction, while scarce neutrophils may promote more aggressive infection.

Conclusions:

• Neutrophil interaction triggers a branching mechanism in Aspergillus fumigatus, allowing evasion and continued invasion.
• This fungal behavior has significant implications for infections in patients with neutropenia (low neutrophil count).
• Targeting fungal branching presents a potential new therapeutic strategy for invasive aspergillosis.