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Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
Published on: December 19, 2014
The outcome of Cryptococcus neoformans intracellular pathogenesis in human monocytes
Mauricio Alvarez1, Tamika Burn, Yong Luo
1Department of Microbiology and Immunology and Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA. maalvare@aecom.yu.edu
Background:
Cryptococcus neoformans is an encapsulated yeast that is a facultative intracellular pathogen. The interaction between macrophages and C. neoformans is critical for extrapulmonary dissemination of this pathogenic yeast. C. neoformans can either lyse macrophages or escape from within them through a process known as phagosomal extrusion. However, most studies of intracellular pathogenesis have been made with mouse cells and their relevance to human infection is uncertain. In this study we extended studies of C. neoformans-macrophage cellular interaction/s to human peripheral blood monocytes.
Results:
This study demonstrated that C. neoformans can shed polysaccharide within human monocytes, spread from cell to cell, and be extruded from them. Furthermore, human monocytes responded to ingestion of C. neoformans with cell cycle progression from G1 to S.
Conclusion:
Similarities between mouse and human cells support the suitability of mouse cells for the study of intracellular pathogenesis mechanisms. Given that these hosts diverged over 70 million years ago, the similar pathogenic strategies for C. neoformans in murine and human cells supports the hypothesis that the mechanism that underlies the mammalian intracellular pathogenesis of C. neoformans originated from interactions with a third host, possibly soil amoeboid predators, before the mammalian radiation.
Insights
Cryptococcus neoformans can infect human monocytes, shedding polysaccharide and spreading between cells. These findings in human cells validate mouse models for studying fungal pathogenesis.
Area of Science:
- Mycology
- Immunology
- Cell Biology
Background:
- Cryptococcus neoformans is a yeast pathogen that infects macrophages.
- Extrapulmonary dissemination relies on macrophage interaction.
- Pathogenesis studies primarily used mouse cells, with uncertain human relevance.
Purpose of the Study:
- Investigate Cryptococcus neoformans-macrophage interactions in human monocytes.
- Determine if C. neoformans pathogenesis mechanisms in humans mirror those in mice.
Main Methods:
- Utilized human peripheral blood monocytes for cellular interaction studies.
- Observed C. neoformans behavior within human monocytes.
Main Results:
- Demonstrated C. neoformans shedding polysaccharide within human monocytes.
- Showed C. neoformans spreading cell-to-cell and undergoing phagosomal extrusion from human monocytes.
- Observed human monocyte cell cycle progression (G1 to S) upon C. neoformans ingestion.
Conclusions:
- Human and mouse cells exhibit similar C. neoformans pathogenic strategies.
- Mouse models are suitable for studying intracellular pathogenesis of C. neoformans.
- Pathogenic mechanisms likely predate mammalian evolution, possibly originating from interactions with amoeboid predators.
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