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

Author

Listed:
  • Yifan Wu

    (Baylor College of Medicine, One Baylor Plaza
    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
    Baylor College of Medicine, One Baylor Plaza
    Baylor College of Medicine, One Baylor Plaza)

  • Hui-Ying Tung

    (Baylor College of Medicine, One Baylor Plaza
    Baylor College of Medicine, One Baylor Plaza)

  • Cameron T. Landers

    (Baylor College of Medicine, One Baylor Plaza
    Medicine, Baylor College of Medicine, One Baylor Plaza
    Baylor College of Medicine, One Baylor Plaza)

  • Yuwei Liu

    (Neuroscience, Baylor College of Medicine, One Baylor Plaza
    Baylor College of Medicine, One Baylor Plaza
    Baylor College of Medicine, One Baylor Plaza)

  • Brittany G. Seman

    (University of Maine)

  • Robert T. Wheeler

    (University of Maine
    University of Maine)

  • Mauro Costa-Mattioli

    (Neuroscience, Baylor College of Medicine, One Baylor Plaza
    Baylor College of Medicine, One Baylor Plaza
    Baylor College of Medicine, One Baylor Plaza)

  • Farrah Kheradmand

    (Baylor College of Medicine, One Baylor Plaza
    Baylor College of Medicine, One Baylor Plaza
    Medicine, Baylor College of Medicine, One Baylor Plaza
    Michael E. DeBakey VA Center for Translational Research on Inflammatory Diseases)

  • Hui Zheng

    (Baylor College of Medicine, One Baylor Plaza
    Baylor College of Medicine, One Baylor Plaza
    Baylor College of Medicine, One Baylor Plaza)

  • David B. Corry

    (Baylor College of Medicine, One Baylor Plaza
    Baylor College of Medicine, One Baylor Plaza
    Medicine, Baylor College of Medicine, One Baylor Plaza
    Michael E. DeBakey VA Center for Translational Research on Inflammatory Diseases)

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.

Suggested Citation

  • 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 & David B. Cor, 2019. "Microglia and amyloid precursor protein coordinate control of transient Candida cerebritis with memory deficits," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-07991-4
    DOI: 10.1038/s41467-018-07991-4
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