Hyphal swelling induced in the phagosome of macrophages

Summary

When Candida albicans yeast cells are engulfed by immune cells called macrophages, they transform into thread-like hyphae. Researchers discovered that these hyphae sometimes develop swollen, bulbous compartments rather than maintaining their normal shape. Surprisingly, these swollen fungal cells survive much better inside the hostile macrophage environment than normal-shaped hyphae. This swelling appears to be a clever survival strategy that helps the fungus resist being killed by the immune system.

Background

Candida albicans is a morphologically plastic fungal pathogen that forms hyphae within macrophages as part of infection. Macrophages are key immune cells that attempt to kill internalized fungi through hostile phagosomal environments. Understanding the dynamic interactions between fungal morphology and macrophage immunity is critical for comprehending fungal pathogenesis.

Objective

The study investigated morphological changes in Candida albicans hyphae during macrophage phagocytosis and determined whether hyphal swelling provides a survival advantage within the macrophage phagolysosome. The researchers examined whether swollen hyphal compartments retain viability better than non-swollen compartments.

Results

Internalized C. albicans hyphae formed swollen apical and sub-apical compartments that ceased polarized elongation and became bulbous. Swollen compartments showed significantly reduced permeabilization to LysoTracker Red, indicating enhanced viability compared to non-swollen compartments (15.33% vs 38% cell death). Cell wall analysis revealed higher β-glucan and chitin exposure in internalized filaments, suggesting active remodeling.

Conclusion

Hyphal swelling within macrophage phagolysosomes represents an adaptive morphological response that promotes fungal survival in the hostile intracellular environment. The formation of swollen compartments with altered cell wall composition may constitute a previously unrecognized immune evasion mechanism. This swelling phenotype contributes to the ability of C. albicans to persist within macrophages and resist macrophage-mediated killing.
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