Both the lectin and alternative pathways of complement activation play roles in Cryptococcus gattii infection

Abstract

Complement is a cascade of serum proteins involved in opsonization, membrane lysis, and anaphylaxis. Complement can be activated through three pathways: classical, alternative, and lectin. It has been shown that pathogenic Cryptococcus species activate the alternative pathway of the complement cascade, while the polysaccharide capsule blocks activation of the classical pathway. While human mannose binding lectin (MBL) has been reported to not bind to Cryptococcus, no published studies have characterized murine MBL binding to Cryptococcus. Using flow cytometry, we analyzed C3 deposition on C. gattii in the presence of serum from C57BL/6J (intact complement pathways), factor B‐deficient (lacking alternative pathway), and MBL‐deficient mice (lacking lectin pathway), and found that complement activation occurred via both the alternative and the lectin pathways. When mice were infected intravenously with C. gattii, C3‐ and factor B‐deficient mice died significantly faster than C57BL/6J mice and showed higher fungal burdens in the lungs. Radiolabeled heat‐killed C. gattii injected intravenously cleared rapidly in C57BL/6J mice. However, in factor B‐deficient and C3‐deficient mice, organisms cleared much less rapidly, indicating a role for complement activation in organism clearance.NIH R01 AI51415‐5