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.
Highlights
Bloodborne infections with Candida albicans are an increasingly recognized complication of modern medicine
We further show that the cerebritis is characterized by a unique pathologic structure, the fungal-induced glial granuloma, that is marked by focal gliosis surrounding fungal cells and the deposition of both amyloid precursor protein (APP) and amyloid beta peptides, that latter which promote anti-fungal immunity
We discovered that a single injection of 25,000 viable cells of C. albicans into wild-type C57BL/6 mice produced a transient cerebral infection that was detectable 4 days post challenge, but largely cleared by day 10 (Fig. 1a, b)
Summary
Bloodborne infections with Candida albicans are an increasingly recognized complication of modern medicine. Fungal sepsis/hematogenous dissemination does not elicit allergic responses, which instead appear to be reserved to prevent fungal dissemination from mucosal sites, and rapidly attenuate in favor of type 1 and type 17 immunity when dissemination occurs, at least in the context of hyphal fungal disease due to Aspergillus spp.[13,14,15]. In part, such fungal-immune system cross-talk involves two-way interactions with innate immune cells that attenuate fungal, especially Candida, virulence, and regulate adaptive immunity[16,17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
