Cryptococcal Yeast Cells Invade the Central Nervous System via Transcellular Penetration of the Blood-Brain Barrier

• DOI: 10.1128/iai.72.9.4985-4995.2004
• Publication Date: 2004-08-21T03:12:22Z
• Authors: Yun C. Chang; Monique F. Stins; Michael J. McCaffery; Georgina F. Miller; Dan R. Pare; Tapen Dam; Maneesh Paul-Saty...; Kwang Sik Kim; Kyung J. Kwon-Chung
• Keywords: Transcellular; Parenchyma

Cryptococcal meningoencephalitis develops as a result of hematogenous dissemination inhaled Cryptococcus neoformans from the lung to brain. The mechanism(s) by which C. crosses blood-brain barrier (BBB) is key unresolved issue in cryptococcosis. We used both an vivo mouse model and vitro human BBB investigate cryptococcal association with traversal BBB. Exposure brain microvascular endothelial cells (HBMEC) triggered formation microvillus-like membrane protrusions within 15 30 min. Yeast adhered were internalized HBMEC, they crossed HBMEC monolayers via transcellular pathway without affecting monolayer integrity. histopathology brains obtained after intravenous injection showed that yeast either associated or escaped capillary vessels into neuropil 3 h. was found parenchyma away 22 Association choroid plexus, however, not detected during up 10 days observation. Our findings indicate invade central nervous system crossing endothelium