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

Yifan Wu, Shuqi Du, Jennifer L. Johnson, Hui-Ying Tung, Cameron T. Landers, Yuwei Liu, Brittany G. Seman, Robert T. Wheeler, Mauro Costa-Mattioli, Farrah Kheradmand, Hui Zheng and David B. Corry ()
Additional contact information
Yifan Wu: Baylor College of Medicine, One Baylor Plaza
Shuqi Du: Baylor College of Medicine, One Baylor Plaza
Jennifer L. Johnson: Neuroscience, Baylor College of Medicine, One Baylor Plaza
Hui-Ying Tung: Baylor College of Medicine, One Baylor Plaza
Cameron T. Landers: Baylor College of Medicine, One Baylor Plaza
Yuwei Liu: Neuroscience, Baylor College of Medicine, One Baylor Plaza
Brittany G. Seman: University of Maine
Robert T. Wheeler: University of Maine
Mauro Costa-Mattioli: Neuroscience, Baylor College of Medicine, One Baylor Plaza
Farrah Kheradmand: Baylor College of Medicine, One Baylor Plaza
Hui Zheng: Baylor College of Medicine, One Baylor Plaza
David B. Corry: Baylor College of Medicine, One Baylor Plaza

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-018-07991-4

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