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Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
11:07

Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans

Published on: December 19, 2014

Cryptococcal yeast cells invade the central nervous system via transcellular penetration of the blood-brain barrier

Yun C Chang1, Monique F Stins, Michael J McCaffery

  • 1Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Infection and Immunity
|August 24, 2004
PubMed

Insights

Cryptococcus neoformans invades the brain by crossing the blood-brain barrier (BBB) through a transcellular route. This study reveals the mechanism of fungal entry into the central nervous system.

Area of Science:

  • Neuroscience
  • Infectious Diseases
  • Microbiology

Background:

  • Cryptococcal meningoencephalitis is a severe fungal infection.
  • The mechanism of Cryptococcus neoformans crossing the blood-brain barrier (BBB) remains unclear.

Purpose of the Study:

  • To investigate how C. neoformans interacts with and crosses the BBB.
  • To elucidate the pathway of fungal invasion into the central nervous system.

Main Methods:

  • Utilized an in vivo mouse model and an in vitro human BBB model.
  • Observed yeast cell interaction with human brain microvascular endothelial cells (HBMEC).
  • Analyzed histopathology of mouse brains after C. neoformans injection.

Main Results:

  • C. neoformans induced membrane protrusions and adhered to HBMEC.
  • Yeast cells crossed HBMEC monolayers via a transcellular pathway without compromising integrity.
  • In mice, C. neoformans associated with or escaped brain capillaries within 3 hours, reaching the parenchyma by 22 hours.

Conclusions:

  • C. neoformans invades the central nervous system by transcellularly crossing the BBB endothelium.
  • The choroid plexus was not identified as an entry point during the study period.

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