Mechanisms of Candida albicans Trafficking to the Brain

PLoS Pathogens

Yaoping Liu¹  Norma V. Solis¹  Rahul Mittal²  Nemani V. Prasadarao²  Scott G. Filler³ 

[1] Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States of America;Division of Infectious Diseases, The Saban Research Institute, Childrens Hospital Los Angeles, California, United States of America;Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America

关键词: C;    ida albicans;    Endocytosis;    Mouse models;    Endothelial cells;    Saccharomyces cerevisiae;    Fungal diseases;    C;    idiasis;    Small interfering RNAs;   

DOI  :  10.1371/journal.ppat.1002305

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

During hematogenously disseminated disease, Candida albicans infects most organs, including the brain. We discovered that a C. albicans vps51Δ/Δ mutant had significantly increased tropism for the brain in the mouse model of disseminated disease. To investigate the mechanisms of this enhanced trafficking to the brain, we studied the interactions of wild-type C. albicans and the vps51Δ/Δ mutant with brain microvascular endothelial cells in vitro. These studies revealed that C. albicans invasion of brain endothelial cells is mediated by the fungal invasins, Als3 and Ssa1. Als3 binds to the gp96 heat shock protein, which is expressed on the surface of brain endothelial cells, but not human umbilical vein endothelial cells, whereas Ssa1 binds to a brain endothelial cell receptor other than gp96. The vps51Δ/Δ mutant has increased surface expression of Als3, which is a major cause of the increased capacity of this mutant to both invade brain endothelial cells in vitro and traffic to the brain in mice. Therefore, during disseminated disease, C. albicans traffics to and infects the brain by binding to gp96, a unique receptor that is expressed specifically on the surface of brain endothelial cells.

【 授权许可】

CC BY