Role of complement in protection against Cryptococcus gattii infection

Area of Science:

• Immunology
• Microbiology
• Infectious Diseases

Background:

• The alternative pathway of complement activation is known to protect against Cryptococcus neoformans infection.
• Cryptococcus gattii exhibits less efficient alternative pathway activation compared to C. neoformans in vitro.
• The role of complement in C. gattii infection in vivo remains largely uncharacterized.

Purpose of the Study:

• To investigate the role of complement activation in host defense against Cryptococcus gattii infection in a murine model.
• To determine if the alternative pathway is the primary complement-mediated protective mechanism against C. gattii.

Main Methods:

• Utilized mice deficient in complement components (factor B and C3) to assess survival and fungal burden.
• Employed histopathology to evaluate fungal dissemination and tissue damage in the lungs.
• Tracked the fate of radiolabeled C. gattii organisms to measure clearance efficiency.
• Assessed the impact of complement-deficient serum on macrophage-mediated killing of C. gattii in vitro.

Main Results:

• Factor B-deficient mice exhibited increased mortality, while C3-deficient mice showed even more rapid death, suggesting non-alternative pathway complement involvement.
• Complement-deficient mice (both C3 and factor B) displayed significantly higher fungal burdens in the lungs compared to wild-type controls.
• Reduced clearance of radiolabeled C. gattii was observed in factor B- and C3-deficient mice.
• Macrophage killing of C. gattii was impaired when using serum from complement-deficient mice.

Conclusions:

• Complement activation is essential for host survival during Cryptococcus gattii infection.
• Protection against C. gattii involves complement pathways beyond the alternative pathway.
• Impaired complement function leads to increased fungal burden and mortality, highlighting complement's critical role in host defense.