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

Published on: December 19, 2014

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The Outcome of the Cryptococcus neoformans-Macrophage Interaction Depends on Phagolysosomal Membrane Integrity

Carlos M De Leon-Rodriguez1, Diego C P Rossi2, Man Shun Fu2

  • 1Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY 10461.

Journal of Immunology (Baltimore, Md. : 1950)
|June 3, 2018
PubMed

Insights

Cryptococcus neoformans induces phagolysosomal membrane permeabilization (PMP) in macrophages, linking PMP to apoptosis. Phospholipase B1 and capsular enlargement are key factors in PMP development.

Area of Science:

  • Mycology
  • Immunology
  • Cell Biology

Background:

  • Cryptococcus neoformans is a global fungal pathogen.
  • It survives and replicates within macrophage phagolysosomes.
  • C. neoformans induces phagolysosomal membrane permeabilization (PMP), but mechanisms and consequences are unclear.

Purpose of the Study:

  • To investigate the mechanisms and consequences of PMP induced by C. neoformans in macrophages.
  • To determine the role of phospholipase B1 in PMP.
  • To explore the relationship between PMP, apoptosis, and macrophage function.

Main Methods:

  • Flow cytometry to measure PMP in infected macrophages.
  • Utilized cell viability markers and LysoTracker.
  • Infection with wild-type, Δplb1 mutant, and complemented C. neoformans strains.

Main Results:

  • PMP correlated with macrophage apoptosis.
  • Reduced PMP was observed with the C. neoformans Δplb1 mutant, implicating phospholipase B1.
  • Capsular enlargement was identified as a potential cause of membrane damage.
  • Apoptotic macrophages lost phagolysosomal acidity.
  • PMP induction promoted lytic exocytosis.

Conclusions:

  • Phospholipase B1 and capsular enlargement are virulence factors contributing to PMP.
  • PMP is closely associated with macrophage apoptosis and altered phagolysosomal function.
  • Modulation of PMP is critical for C. neoformans-macrophage interaction outcomes.

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