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Differential host susceptibility to intracerebral infections with Candida albicans and Cryptococcus neoformans
E Blasi1, R Barluzzi, R Mazzolla
1Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Italy.
Abstract:
To investigate the immune defense mechanisms employed against fungi in the brain, mice were experimentally infected by intracerebral inoculation of Candida albicans or Cryptococcus neoformans. Parameters such as median survival time and numbers of yeast cells in the brains were assessed for naive and immunomodulated mice. We found that no mice survived either C. albicans or C. neoformans challenge at doses of > or = 10(6) yeast cells per mouse. However, when the inoculum size was decreased (< or = 10(5) yeast cells per mouse), C. albicans was no longer lethal (100% survival), whereas 100 and 70% of the mice still succumbed to challenge doses of 10(4) and 10(3) C. neoformans yeast cells, respectively. Pharmacological manipulation and transfer experiments revealed that the myelomonocytic compartment had a minor role against C. neoformans but was deeply involved in the control of intracerebral C. albicans infection. By counting the number of yeast cells in the brains of naive and immunomodulated animals, we established that, unlike C. albicans, C. neoformans remained essentially in the brain, where massive colonization and damage occurred whether naive or immunomodulated defense mechanisms were employed by the host. Overall, these data suggest that the differential role of the myelomonocytic compartment, together with the diverse tropisms of the two fungi, can explain the different development and outcome of intracerebral C. albicans and C. neoformans infections.
Insights
The myelomonocytic immune compartment is crucial for controlling brain infections by Candida albicans but not Cryptococcus neoformans. Fungal tropism and immune cell roles dictate infection outcomes.
Area of Science:
- Neuroscience
- Immunology
- Mycology
Background:
- Fungal infections of the brain, such as those caused by Candida albicans and Cryptococcus neoformans, pose significant health risks.
- Understanding the brain's immune defense mechanisms against these fungi is critical for developing effective treatments.
Purpose of the Study:
- To investigate the distinct immune defense mechanisms against fungal brain infections.
- To compare the roles of the myelomonocytic compartment in controlling Candida albicans and Cryptococcus neoformans infections in the brain.
Main Methods:
- Experimental intracerebral inoculation of mice with Candida albicans or Cryptococcus neoformans.
- Assessment of survival rates and fungal burden in the brain under varying inoculum sizes and immunomodulation.
- Pharmacological manipulation and cell transfer experiments to evaluate the myelomonocytic compartment's role.
Main Results:
- Candida albicans infection was non-lethal at lower doses (< or = 10(5) yeast cells/mouse) with 100% survival.
- Cryptococcus neoformans remained lethal even at lower doses (10(4) and 10(3) yeast cells/mouse), causing 100% and 70% mortality, respectively.
- The myelomonocytic compartment was vital for controlling C. albicans but played a minor role against C. neoformans, which showed extensive brain colonization and damage.
Conclusions:
- The differential involvement of the myelomonocytic compartment significantly impacts the outcome of fungal brain infections.
- The distinct tropisms of C. albicans and C. neoformans contribute to the varied pathogenesis observed in the brain.
- These findings highlight the specific immune strategies required for combating different fungal pathogens within the central nervous system.