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Infection and Immunity, July 2001, p. 4536-4544, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4536-4544.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Traversal of Candida albicans across Human Blood-Brain Barrier In Vitro

Ambrose Y. Jong,1,* Monique F. Stins,2 Sheng-He Huang,2 Steven H. M. Chen,1 and Kwang Sik Kim2

Divisions of Hematology-Oncology1 and Infectious Diseases,2 Childrens Hospital Los Angeles, Los Angeles, California 90027

Received 10 October 2000/Returned for modification 14 December 2000/Accepted 13 March 2001

Candida albicans is an opportunistic pathogen, which primarily affects neonates and immunocompromised individuals. The pathogen can invade the central nervous system, resulting in meningitis. At present, the pathogenesis of C. albicans meningitis is unclear. We used an in vitro model of the human blood-brain barrier to investigate the interaction(s) of C. albicans with human brain microvascular endothelial cells (BMEC). Binding of C. albicans to human BMEC was time and inoculum dependent. Invasion of C. albicans into human BMEC was demonstrated by using an enzyme-linked immunosorbent assay based on fluorescent staining of C. albicans with calcoflour. In contrast, avirulent Candida mutant strains and nonpathogenic yeast Saccharomyces cerevisiae were not able to bind and invade human BMEC. Morphological studies revealed that on association with human BMEC, C. albicans formed germ tubes and was able to bud intracellularly. Transmission electron microscopy showed various stages of C. albicans interactions with human BMEC, e.g., pseudopod-like structures on human BMEC membrane and intracellular vacuole-like structures retaining C. albicans. Of interest, C. albicans was able to bud and develop pseudohyphae inside human BMEC without apparent morphological changes of the host cells. In addition, C. albicans penetrates through human BMEC monolayers without a detectable change in transendothelial electrical resistance and inulin permeability. This is the first demonstration that C. albicans is able to adhere, invade, and transcytose across human BMEC without affecting monolayer integrity. A complete understanding of the interaction(s) of C. albicans with human BMEC should contribute to the understanding of the pathogenic mechanism(s) of C. albicans meningitis.

* Corresponding author. Mailing address: Division of Hematology-Oncology, MS 57, Childrens Hospital Los Angeles, Los Angeles, CA 90027. Phone: (323) 669-5647. Fax: (323) 953-9940. E-mail: ajong{at}chla.usc.edu.

Infection and Immunity, July 2001, p. 4536-4544, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4536-4544.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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