Persistence within dendritic cells marks an antifungal evasion and dissemination strategy of Aspergillus terreus

Area of Science:

• Medical Mycology
• Immunology
• Infectious Diseases

Background:

• Aspergillus terreus is an airborne fungal pathogen causing invasive aspergillosis in immunocompromised individuals.
• A. terreus infections exhibit high dissemination rates and poor antifungal treatment response compared to Aspergillus fumigatus.

Purpose of the Study:

• To compare the interactions of Aspergillus terreus and Aspergillus fumigatus conidia with dendritic cells (DCs).
• To elucidate the mechanisms behind A. terreus' immune evasion and treatment resistance.

Main Methods:

• Co-incubation of fungal conidia (A. terreus and A. fumigatus) with MUTZ-3-derived dendritic cells (DCs).
• Assessment of conidial survival, intracellular germination, and immune cell activation markers (e.g., CD80, CD83, CD54, MHCII, CCR7).
• Measurement of cytokine production (pro-inflammatory and T-cell stimulating) by DCs.

Main Results:

• A. terreus conidia persisted and survived long-term within DCs, while A. fumigatus conidia rapidly escaped.
• Intracellular A. terreus conidia were protected from antifungal agents, unlike A. fumigatus conidia.
• A. terreus conidia demonstrated significantly lower immunogenicity, failing to trigger DC activation or pro-inflammatory cytokine production.

Conclusions:

• A. terreus conidia evade immune surveillance by persisting within DCs, contributing to treatment failure and dissemination.
• Immune cell persistence is a potential mechanism underlying the clinical challenges posed by A. terreus infections.
• Targeting fungal persistence within immune cells may offer new therapeutic strategies against invasive aspergillosis.