Histopathological features of two strains of Cryptococcus neoformans var. gattii with different virulence

Background: Cryptococcosis is a deep-seated mycosis present worldwide; most cases in Japan are caused by inhalation of Cryptococcus neoformans var. neoformans. C. neoformans var. gattii infection is only sporadic in Japan, and, consequently, there are few studies of C. neoformans var. gattii in the Japanese literature. In order to better understand the pathophysiology of C. neoformans var. gattii infection, we compared the biological nature and histopathology of pulmonary lesions caused by 2 strains of C. neoformans var. gattii that had greatly differing virulence. Methods: Mortality in mice was compared in 2 isolates of C. neoformans var. neoformans from human (TIMM0362 and TIMM0372), 2 isolates of C. neoformans var. neoformans from koala (TIMM4920 and TIMM4922), and 2 isolates of C. neoformans var. gattii from koala (TIMM4097 and TIMM4903). Then, capsule thickness, carbohydrate assimilation, growth temperature, growth rate at 37°C, hydrolytic activity (urease, protease, and phospholipase), and phenoloxydase activity were examined in two C. neoformans var. gattii isolates (TIMM4097 and TIMM4903) that showed the greatest difference in mortality rate in infected mice. Finally, we compared histopathological and morphometric data from pulmonary lesions induced by tracheal infection by these 2 strains of C. neoformans var. gattii. Results: Although the 2 strains of C. neoformans var. gattii differed in virulence, there was little difference in their biological nature. However, a substantial difference in the histological features of pulmonary lesions caused by these strains was noted. The low virulent strain induced diffuse proliferation over the lung, with much lesser inflammatory response; the high virulent strain caused focal and expansive proliferation, with stratification of septa compressed at the periphery of each focus. Conclusion: Although no significant difference in biological nature was found between the 2 strains of C. neoformans var. gattii, our results suggest that the distinct difference in histological features induced by these strains can be attributed to a difference in their capacity to adhere to the epithelial cells of alveolar septa.