Human neutrophils produce extracellular traps against Paracoccidioides brasiliensis

Area of Science:

• Immunology
• Mycology
• Microbiology

Background:

• Neutrophils are key immune cells for host defense against pathogens.
• Neutrophil Extracellular Traps (NETs) are crucial for combating fungal infections like Aspergillus, Candida, and Cryptococcus.
• The role of NETs in response to Paracoccidioides brasiliensis remained uninvestigated.

Purpose of the Study:

• To investigate the capacity of human neutrophils to produce NETs against Paracoccidioides brasiliensis.
• To elucidate the mechanisms regulating NET formation in response to P. brasiliensis, including the role of reactive oxygen species (ROS) and fungal morphotype.
• To assess the fungicidal efficacy of NETs against P. brasiliensis.

Main Methods:

• Human neutrophils were stimulated with conidia and yeast forms of P. brasiliensis.
• NET production was assessed in the presence of NADPH oxidase inhibitor (DPI), cytochalasin D, and IFN-γ.
• A P. brasiliensis mutant strain with reduced alternative oxidase expression was used.
• Fungal burden was quantified using colony-forming unit (c.f.u.) assays.

Main Results:

• Human neutrophils successfully generated NETs against both conidia and yeast forms of P. brasiliensis.
• NET formation against yeast was partially dependent on ROS, while conidia-induced NETs were ROS-independent.
• Cytochalasin D and IFN-γ did not influence NET production.
• A P. brasiliensis mutant with lower alternative oxidase expression induced higher NET levels.
• NETs did not significantly reduce P. brasiliensis fungal burden.

Conclusions:

• Human neutrophils produce NETs against P. brasiliensis in a manner dependent on fungal morphotype and ROS production.
• NET formation against P. brasiliensis is not a fully effective mechanism for fungal clearance.
• Further research is needed to understand the complex interactions between neutrophils, NETs, and P. brasiliensis.