In vivo clearance of glucuronoxylomannan, the major capsular polysaccharide of Cryptococcus neoformans:: A critical role for tissue macrophages

Cryptococcus neoformans produces a life-threatening meningitis in patients who are immunocompromised by AIDS. A striking feature of cryptococcosis in AIDS is high serum levels of the major capsular polysaccharide, glucuronoxylomannan (GXM). Soluble GXM has numerous biologic activities that may contribute to the pathogenesis of infection. The objective of the study was to further understand in vivo processing of GXM. Mice were injected intravenously with GXM, and the tissue distribution was determined. A macrophage suicide technique that used liposome-encapsulated dichloromethylene diphosphonate determined the role of macrophages. GXM was cleared from serum with a half-life of 24-48 h but was retained for an indefinite period in tissues rich in cells of the mononuclear phagocyte system. Ablation of macrophages decreased GXM in the liver and spleen and increased serum GXM. The results identify a key role for macrophages in the clearance of GXM from serum and identify macrophages as a long-term reservoir for storage.