Activation of the alternative complement pathway by Fonsecaea pedrosoi

Area of Science:

• Immunology
• Microbiology
• Complement System Biology

Background:

• Fonsecaea pedrosoi is a fungus implicated in human infections.
• The complement system is a crucial part of innate immunity.
• Understanding how pathogens interact with the complement system is vital for developing therapeutic strategies.

Purpose of the Study:

• To investigate the interaction between Fonsecaea pedrosoi and the human complement system.
• To determine the specific pathway of complement activation induced by F. pedrosoi.
• To assess the generation of complement anaphylatoxin C5a during this activation.

Main Methods:

• Human sera were incubated with Fonsecaea pedrosoi.
• Complement activation was assessed by measuring C3 conversion using immunoelectrophoresis.
• Generation of C5a was quantified using radioimmunoassay.
• Functional assays involved heat-inactivated serum, EDTA-chelated serum, and serum depleted of Factor B.
• Classical pathway activation was blocked using Mg++-EGTA.

Main Results:

• Incubation of human sera with F. pedrosoi resulted in C3 conversion and C5a generation.
• These effects were abolished in serum lacking complement activity (heat-inactivated, EDTA-chelated) or deficient in Factor B.
• Complement activation occurred independently of the classical pathway, as demonstrated by Mg++-EGTA inhibition.
• F. pedrosoi specifically activates the alternative complement pathway.

Conclusions:

• Fonsecaea pedrosoi activates the human complement system predominantly via the alternative pathway.
• The activation results in the production of C5a, suggesting a role in inflammatory responses during F. pedrosoi infections.
• These findings contribute to understanding the immunobiology of chromoblastomycosis and related fungal diseases.