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Microglia and amyloid precursor protein coordinate control of transient Candida cerebritis with memory deficits

Wu Y, Du S, Johnson JL, Tung HY, Landers CT, Liu Y, Seman BG, Wheeler RT, Costa-Mattioli M, Kheradmand F, Zheng H, Corry DB (2019) Nat Commun.  2019 Jan 4;10(1): 58. doi: 10.1038/s41467-018-07991-4. 

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Abstract:

Bloodborne infections with Candida albicans are an increasingly recognized complication of modern medicine.

Here, we present a mouse model of low-grade candidemia to determine the effect of disseminated infection on cerebral function and relevant immune determinants. We show that intravenous injection of 25,000 C. albicans cells causes a highly localized cerebritis marked by the accumulation of activated microglial and astroglial cells around yeast aggregates, forming fungal-induced glial granulomas. Amyloid precursor protein accumulates within the periphery of these granulomas, while cleaved amyloid beta (Aβ) peptides accumulate around the yeast cells. CNS-localized C. albicans further activate the transcription factor NF-κB and induce production of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor (TNF), and Aβ peptides enhance both phagocytic and antifungal activity from BV-2 cells. Mice infected with C. albicans display mild memory impairment that resolves with fungal clearance.

Our results warrant additional studies to understand the effect of chronic cerebritis on cognitive and immune function.

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