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Traversal of Candida albicans across human blood-brain barrier in vitro

A Y Jong1, M F Stins, S H Huang

  • 1Divisions of Hematology-Oncology, Childrens Hospital Los Angeles, Los Angeles, California 90027, USA. ajong@chla.usc.edu

Infection and Immunity
|June 13, 2001
PubMed

Insights

Candida albicans can invade the human blood-brain barrier by adhering to and penetrating brain microvascular endothelial cells (BMEC). This study reveals how the pathogen crosses this barrier without damaging it, offering insights into meningitis pathogenesis.

Area of Science:

  • Microbiology
  • Pathogenesis
  • Neuroscience

Background:

  • Candida albicans is an opportunistic pathogen causing infections, particularly in neonates and immunocompromised individuals.
  • C. albicans meningitis is a severe complication, but its pathogenesis, especially crossing the blood-brain barrier, remains poorly understood.

Purpose of the Study:

  • To investigate the interaction between Candida albicans and human brain microvascular endothelial cells (BMEC) using an in vitro blood-brain barrier model.
  • To elucidate the mechanisms of C. albicans invasion and transmigration across the human blood-brain barrier.

Main Methods:

  • Utilized an in vitro human blood-brain barrier model with BMEC.
  • Employed enzyme-linked immunosorbent assay with fluorescent staining to detect C. albicans invasion.
  • Conducted morphological studies and transmission electron microscopy to visualize cellular interactions.
  • Assessed monolayer integrity via transendothelial electrical resistance and inulin permeability measurements.

Main Results:

  • C. albicans demonstrated time- and inoculum-dependent binding and invasion of BMEC.
  • Avirulent Candida strains and Saccharomyces cerevisiae did not bind or invade BMEC.
  • Intracellular budding, germ tube formation, and pseudohyphae development by C. albicans were observed within BMEC.
  • C. albicans transmigrated across BMEC monolayers without compromising barrier integrity (transendothelial electrical resistance and inulin permeability).

Conclusions:

  • Candida albicans can adhere to, invade, and transcytose across human BMEC without detectable damage to the blood-brain barrier.
  • These findings provide the first demonstration of C. albicans breaching the human blood-brain barrier intact.
  • Understanding these interactions is crucial for elucidating the pathogenic mechanisms of C. albicans meningitis.

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