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Visualizing Non-lytic Exocytosis of Cryptococcus neoformans from Macrophages Using Digital Light Microscopy
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Cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal brain infection

Sheng-He Huang1, Chun-Hua Wu, Yun C Chang

  • 1Division of Infectious Diseases, The Saban Research Institute, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Plos One
|November 13, 2012
PubMed

Insights

Cryptococcus neoformans microvesicles (CnMVs) enhance fungal brain invasion by crossing the blood-brain barrier. These microvesicles accumulate at infection sites, contributing to cryptococcal meningoencephalitis.

Area of Science:

  • Neuroscience
  • Mycology
  • Infectious Diseases

Background:

  • Cryptococcal meningoencephalitis is a prevalent fungal infection of the central nervous system.
  • The mechanisms of brain invasion by Cryptococcus neoformans remain poorly understood.

Purpose of the Study:

  • To investigate the role of Cryptococcus neoformans-derived microvesicles (CnMVs) in brain invasion and pathogenesis.

Main Methods:

  • In vitro studies using human brain microvascular endothelial cells (HBMECs) to assess CnMVs' effect on blood-brain barrier (BBB) traversal.
  • Immunofluorescence imaging to visualize CnMVs interaction with HBMECs and their distribution in infected mouse brains.
  • Analysis of C. neoformans infected mouse brains and cerebrospinal fluid for CnMVs presence and impact on lesions.

Main Results:

  • CnMVs were found to enhance the traversal of the BBB by C. neoformans in vitro.
  • CnMVs demonstrated fusogenic activity with HBMECs, activating membrane rafts.
  • In vivo, CnMVs were detected within and around C. neoformans-induced brain lesions and correlated with substantial pathological changes.

Conclusions:

  • This study provides the first evidence that C. neoformans-derived microvesicles facilitate BBB crossing.
  • CnMVs accumulate at lesion sites, suggesting a significant role in the pathogenesis of cryptococcal meningoencephalitis.

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