Complementary Roles of the Classical and Lectin Complement Pathways in the Defense against Aspergillus fumigatus

Area of Science:

• Immunology
• Microbiology
• Infectious Diseases

Background:

• Aspergillus fumigatus infections pose a high mortality risk, particularly for immunocompromised patients.
• The complement system's role in combating A. fumigatus is crucial but incompletely understood.
• Understanding complement activation pathways is vital for developing effective antifungal strategies.

Purpose of the Study:

• To investigate the roles of the classical, lectin, and alternative complement pathways in response to A. fumigatus.
• To differentiate pathway activation under immunocompetent versus immunocompromised conditions.
• To elucidate the primary complement initiation routes against A. fumigatus.

Main Methods:

• Utilized clinical A. fumigatus conidia with human sera (normal, cord blood, complement-deficient).
• Employed inhibitors targeting C1q, mannose-binding lectin (MBL), and ficolin-2.
• Quantified complement activation products and phagocytosis via flow cytometry.

Main Results:

• The alternative pathway amplifies complement on A. fumigatus but requires classical or lectin pathways for initiation.
• In normal serum, the classical pathway is the primary initiator.
• In C1q-deficient serum and cord blood serum (modeling antibody deficiency), the MBL-lectin pathway becomes the key initiator.
• Lectin pathway activation correlated with lower IgG/IgM binding, indicating its importance in antibody-deficient states.

Conclusions:

• The lectin pathway is the primary complement activator against A. fumigatus in the absence of anti-fungal antibodies.
• The classical pathway is the main activator in individuals with a balanced immune system.
• The lectin pathway plays a critical role in innate immune protection against A. fumigatus, especially in immunocompromised patients.