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Nat Commun. 2019 Jan 4;10(1):58. doi: 10.1038/s41467-018-07991-4.

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

Wu Y1,2, Du S3, Johnson JL4,5,6, Tung HY1,2, Landers CT2,7,8, Liu Y4,5,6, Seman BG9, Wheeler RT9,10, Costa-Mattioli M4,5,6, Kheradmand F1,2,7,11, Zheng H5,6,12, Corry DB13,14,15,16.

Author information

1
Departments of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
2
Biology of Inflammation Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
3
Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
4
Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
5
Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
6
Memory and Brain Research Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
7
Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
8
Translational Biology and Molecular Medicine Program, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
9
Molecular and Biomedical Sciences, University of Maine, Orono, ME, 04469, USA.
10
Graduate School of Biomedical Sciences and Engineering, University of Maine, Orono, ME, 04469, USA.
11
Michael E. DeBakey VA Center for Translational Research on Inflammatory Diseases, Houston, TX, 77030, USA.
12
Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA.
13
Departments of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA. dcorry@bcm.edu.
14
Biology of Inflammation Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA. dcorry@bcm.edu.
15
Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX, 77030, USA. dcorry@bcm.edu.
16
Michael E. DeBakey VA Center for Translational Research on Inflammatory Diseases, Houston, TX, 77030, USA. dcorry@bcm.edu.

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.

PMID:
30610193
PMCID:
PMC6320369
DOI:
10.1038/s41467-018-07991-4
[Indexed for MEDLINE]
Free PMC Article

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