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Phagosome extrusion and host-cell survival after Cryptococcus neoformans phagocytosis by macrophages

Mauricio Alvarez1, Arturo Casadevall

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

Current Biology : CB
|November 7, 2006
PubMed

Insights

Cryptococcus neoformans escapes macrophages via phagosomal extrusion, a novel mechanism allowing pathogen survival and host cell propagation. This discovery reveals a new fungal dissemination strategy.

Area of Science:

  • Mycology
  • Cell Biology
  • Immunology

Background:

  • Cryptococcus neoformans (Cn) is an opportunistic fungal pathogen causing human disease.
  • Cn infects alveolar macrophages, where it can replicate intracellularly and lyse host cells.
  • Cn employs a unique intracellular strategy involving vesicle accumulation and replication within spacious phagosomes.

Purpose of the Study:

  • To investigate the mechanism of Cryptococcus neoformans (Cn) exit from host macrophages.
  • To identify novel pathways for fungal pathogen dissemination.

Main Methods:

  • Observation of Cn-macrophage interactions under specific conditions.
  • Analysis of cellular processes like phagosomal maturation, actin dynamics, and phagosome fusion.
  • Characterization of the phagosomal extrusion phenomenon.

Main Results:

  • Cn can exit macrophages through "phagosomal extrusion," a process where the pathogen is expelled within the phagosome.
  • This exit mechanism allows both the pathogen and host cell to remain viable.
  • Phagosomal extrusion involves phagosomal maturation, actin depolymerization, and homotypic phagosome fusion.

Conclusions:

  • Phagosomal extrusion represents a previously unrecognized mechanism for fungal pathogen escape from mammalian cells.
  • This process facilitates pathogen propagation and potential dissemination.
  • Understanding phagosomal extrusion offers insights into host-pathogen interactions and fungal pathogenesis.

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