Human leukocytes kill Aspergillus nidulans by reactive oxygen species-independent mechanisms

Area of Science:

• Immunology
• Mycology
• Infectious Diseases

Background:

• Invasive aspergillosis poses a significant threat to patients with chronic granulomatous disease (CGD).
• While Aspergillus fumigatus is common, Aspergillus nidulans infections are disproportionately prevalent in CGD patients.
• The role of NADPH oxidase and reactive oxygen species (ROS) in fungal defense requires clarification, especially concerning A. nidulans.

Purpose of the Study:

• To investigate the role of NADPH oxidase and ROS in host defense against fungal pathogens.
• To clarify the relationship between ROS and A. nidulans in the context of CGD.

Main Methods:

• Murine CGD alveolar macrophages (AM), polymorphonuclear leukocytes (PMN), and peripheral blood mononuclear cells (PBMC) from healthy and CGD individuals were challenged with A. fumigatus or A. nidulans.
• Antifungal effects of ROS were analyzed, including ROS release upon fungal challenge and the impact of NADPH oxidase blockade.
• Conidial germination and hyphal damage were assessed, alongside the microbicidal activity of CGD PMN.

Main Results:

• A. nidulans demonstrated resistance to ROS, unlike A. fumigatus, and did not induce significant ROS release.
• CGD immune cells (PMN, PBMC, AM) effectively arrested A. nidulans conidial germination, comparable to healthy controls.
• NADPH oxidase inhibition reduced A. fumigatus damage but had no effect on A. nidulans hyphae; CGD PMN retained microbicidal activity against A. nidulans.

Conclusions:

• Antifungal resistance to A. nidulans in CGD is not directly mediated by ROS.
• The pathogenesis of A. nidulans infections in CGD cannot be attributed solely to the absence of ROS-mediated microbicidal effects.
• Understanding the in vivo role of NADPH oxidase is crucial for elucidating fungal pathogenesis in CGD.