Cryptococcosis caused by Cryptococcus gattii is a devastating disease of immunocompetent hosts with an incompletely understood pathogenesis. Utilizing an immunoproteomic approach in a naturally occurring koala model of disease, a number of key proteins and pathways are identified in the early and late pathogenesis of cryptococcosis for the first time. In particular, the thioredoxin system appears important in the pathogenesis of cryptococcosis caused by C. gattii VGII.