Despite considerable progress in understanding the pathogenesis of C. neoformans, many questions remain regarding the function of macrophages in normal clearance of infection and the defects present in uncontrolled disease. A critical limitation is the difficulty in interpreting studies using isolated macrophages in the context of the progression of infection.
We have developed a zebrafish model of cryptococcosis and a high-content imaging method that permits the detailed analysis of macrophage interactions with C. neoformans during infection. Using this we are trying to understand why macrophages fail to control cryptococcus and the relevance of intracellular proliferation and the inhibition of phagocytosis by the cryptococcal polysaccharide capsule. See our paper on this here.