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Updated: Feb 8, 2026

Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans

Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans

Published on: December 19, 2014

Microglia detect infections fúngicas a través de componentes capsulares de Cryptococcus neoformans unido a capilares

Chenxu Feng¹, Ge Wang^1,2, Yixuan Wang¹

¹Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

|February 6, 2026

Abstract:

Macrophages are essential for host defense, yet how parenchyma-residing macrophages detect pathogens without direct contact remains unclear. Cryptococcus neoformans is an encapsulated fungal pathogen that infects the brain. Using in situ imaging of mouse model, we showed that brain-resident microglia vigilantly detect capillary-residing C. neoformans prior to its blood-brain barrier transmigration, but are less responsive to nonencapsulated fungi or parenchyma-injected C. neoformans. Microglia migrate to and enwrap leaky capillaries harboring fungi, leading to fungal uptake but not clearance, instead promoting fungal growth. Microglial response is triggered by released capsule components, rather than the assembled capsule. In particular, glucuronoxylomannan (GXM) plays a critical role by activating endothelial cells to release nucleotides which act on microglia P2Y12. Our findings revealed a novel paradigm by which microglia detect pathogens without direct contact, offering new insights for microglia-directed antifungal therapies.

Palabras clave:

microglía Cryptococcus neoformans infecciones fúngicas cápsula fúngica células endoteliales señalización de nucleótidos barrera hematoencefálica terapias antifúngicas

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Biolistic Transformation of a Fluorescent Tagged Gene into the Opportunistic Fungal Pathogen Cryptococcus neoformans

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