In vitro C3 deposition on Cryptococcus capsule occurs via multiple complement activation pathways

► We determined complement deposition on the polysaccharide capsule of Cryptococcus spp. ► C. gattii and C. neoformans activate the alternative pathway. ► We found a role for C4 in the alternative pathway activation by Cryptococcus spp. ► Alternative pathway activation by C. neoformans required both MBL-A and -C. ► Either MBL-A or -C was sufficient for alternative pathway activation by C. gattii.