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Host-Pathogen Interactions and Correlated Factors That Are Affected in Replicative-Aged Cryptococcus neoformans
Vanessa K A Silva1, Sungyun Min1, Kyungyoon Yoo2
1Division of Infectious Diseases, Department of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.
Journal of Fungi (Basel, Switzerland)
|April 26, 2024
Summary
Older Cryptococcus neoformans cells resist immune cells by manipulating phagosome acidity and permeability. Understanding these fungal pathogen strategies aids in developing new antifungal therapies for cryptococcosis.
Area of Science:
- * Mycology and Host-Pathogen Interactions
- * Cellular and Molecular Biology
- * Infectious Diseases and Immunology
Background:
- * Cryptococcus neoformans is a fungal pathogen causing cryptococcosis.
- * Ten-generation-old (10GEN) C. neoformans exhibit increased resistance to host immune cells.
- * Mechanisms underlying this resistance and intracellular survival remain unclear.
Purpose of the Study:
- * To identify factors contributing to the intracellular survival of aged C. neoformans.
- * To investigate host-cell interactions, including phagosomal environment and exocytosis, with aged yeast.
- * To elucidate strategies employed by aged C. neoformans to evade immune clearance.
Main Methods:
- * Flow cytometry and fluorescent microscopy to analyze urease activity, capsule synthesis, and DNA content.
- * Time-lapse imaging to monitor phagosomal acidity, membrane permeability, and vomocytosis in macrophages.
- * Comparative analysis of young versus 10GEN C. neoformans within J774 macrophage models.
Main Results:
- * Aged C. neoformans displayed heightened urease and Golgi activity, with increased G2 phase arrest.
- * Increased phagolysosome pH and membrane permeability were observed with aged yeast.
- * Vomocytosis rates were reduced in aged C. neoformans, suggesting evasion of non-lytic exocytosis.
Conclusions:
- * Aged C. neoformans actively manipulate phagosomal pH and permeability to survive within macrophages.
- * These adaptations contribute to cryptococcosis pathogenesis by resisting immune killing.
- * Understanding these host-pathogen interactions offers potential for novel antifungal drug development.
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