Abstract
Granulomatous inflammation is the dominant histopathologic feature of cryptococcal infection. Intravenous inoculation of encapsulated Cryptococcus neoformans cells produces granulomas in the rat liver, spleen and lung, where the granulomas play a crucial role in containment and clearance of Cryptococcus cells. In these sites the resident macrophages were the major cell type composed of the granuloma, while the monocyte-derived macrophages predominated in the intravascular granulomas. Enhanced expression of ICAM-1 on the surface of endothelial cells was likely to mediate the formation of intravascular granulomas in the process of disseminated infection. In the CNS an induced expression of class II MHC and CD11b/c antigens was observed as the earliest indication of microglial activation, which preferentially occurred in the white matter. Granuloma macrophages also expressed both these immunophenotypes, although no microglial activation was seen in the vicinity of granulomas in the grey matter. The granulomas in the CNS, however, appeared less effective for clearance of cryptococcal infection because the persistent infection remained even after the extracerebral lesions had totally disappeared. Monocyte-derived, rather than brain-derived, macrophages are believed to be the principal cell population in generating the granulomatous reactions against Cryptococcus cells.
