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Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
Published on: December 19, 2014
Cryptococcal cell morphology affects host cell interactions and pathogenicity
Laura H Okagaki1, Anna K Strain, Judith N Nielsen
1Department of Microbiology, Medical School, University of Minnesota, Minneapolis, Minnesota, United States of America.
Abstract:
Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size of cryptococcal cells is typically 5 to 10 microm. Cell enlargement was observed in vivo, producing cells up to 100 microm. These morphological changes in cell size affected pathogenicity via reducing phagocytosis by host mononuclear cells, increasing resistance to oxidative and nitrosative stress, and correlated with reduced penetration of the central nervous system. Cell enlargement was stimulated by coinfection with strains of opposite mating type, and ste3aDelta pheromone receptor mutant strains had reduced cell enlargement. Finally, analysis of DNA content in this novel cell type revealed that these enlarged cells were polyploid, uninucleate, and produced daughter cells in vivo. These results describe a novel mechanism by which C. neoformans evades host phagocytosis to allow survival of a subset of the population at early stages of infection. Thus, morphological changes play unique and specialized roles during infection.
Insights
Cryptococcus neoformans can dramatically enlarge in vivo, evading immune cells and increasing survival. This fungal cell enlargement is a novel mechanism for pathogen survival during infection.
Area of Science:
- Mycology
- Infectious Diseases
- Cell Biology
Background:
- Cryptococcus neoformans is a significant human fungal pathogen.
- This pathogen typically exists as 5-10 micrometer cells.
- Infection can lead to severe outcomes, including meningoencephalitis.
Purpose of the Study:
- To investigate the phenomenon of cryptococcal cell enlargement in vivo.
- To understand the impact of cell size changes on fungal pathogenicity.
- To elucidate the mechanisms underlying cryptococcal cell enlargement and survival.
Main Methods:
- In vivo observation of Cryptococcus neoformans cell morphology.
- Assessment of phagocytosis by host mononuclear cells.
- Evaluation of resistance to oxidative and nitrosative stress.
- Analysis of fungal cell DNA content and ploidy.
Main Results:
- Cryptococcus neoformans cells enlarged up to 100 microm in vivo.
- Enlarged cells exhibited reduced phagocytosis and increased stress resistance.
- Cell enlargement was associated with decreased central nervous system penetration.
- Enlarged cells were identified as polyploid and uninucleate, capable of producing daughter cells.
Conclusions:
- Cryptococcal cell enlargement is a novel survival mechanism.
- Morphological changes allow evasion of host immune defenses.
- This phenomenon facilitates pathogen survival during early infection stages.
Related Concept Videos
Microbial Morphologies
Overview of Fungi
Fungal Group Zygomycota
Fungal Phylum Microsporidia
Colonisation of Pathogens
Antifungal Agents

