Silva, V.K.A.; Min, S.; Yoo, K.; Fries, B.C. Host–Pathogen Interactions and Correlated Factors That Are Affected in Replicative-Aged Cryptococcus neoformans. J. Fungi2024, 10, 279.
Silva, V.K.A.; Min, S.; Yoo, K.; Fries, B.C. Host–Pathogen Interactions and Correlated Factors That Are Affected in Replicative-Aged Cryptococcus neoformans. J. Fungi 2024, 10, 279.
Silva, V.K.A.; Min, S.; Yoo, K.; Fries, B.C. Host–Pathogen Interactions and Correlated Factors That Are Affected in Replicative-Aged Cryptococcus neoformans. J. Fungi2024, 10, 279.
Silva, V.K.A.; Min, S.; Yoo, K.; Fries, B.C. Host–Pathogen Interactions and Correlated Factors That Are Affected in Replicative-Aged Cryptococcus neoformans. J. Fungi 2024, 10, 279.
Abstract
Cryptococcus neoformans is a facultative intracellular fungal pathogen. Ten-generation-old (10GEN) C. neoformans cells are more resistant to phagocytosis and killing by macrophages than younger daughter cells. However, mechanisms that mediate this resistance and intracellular parasitism are poorly understood. Here, we identified factors important for the intracellular survival of 10GEN C. neoformans, such as urease activity, capsule synthesis, and DNA content using flow cytometry and fluorescent microscopy techniques. Real-time visualization of time-lapse imaging was applied to determine the phagosomal acidity, membrane permeability, and vomocytosis (non-lytic exocytosis) rate in J774 macrophages that phagocytosed C. neoformans of different generational ages. Our results showed that old C. neoformans exhibited higher urease activity, and enhanced capsule formation, which was supported by an increased Golgi complex. In addition, old C. neoformans were more likely to be arrested in the G2 phase, resulting in the occasional formation of aberrant trimera-like cells. To finish, the advanced generational age of the yeast cells slightly reduced vomocytosis events within host cells, which might be associated with increased phagolysosomal pH and membrane permeability. Altogether our results contribute to a better understanding of the strategies used by old C. neoformans to resist phagosomal killing and suggest that old generation C. neoformans intracellular behavior may be driving cryptococcosis pathogenesis.
Biology and Life Sciences, Immunology and Microbiology
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