Related Experiment Videos
Inefficient T cell memory in the brain of mice infected with Candida albicans
M Kretschmar1, A Hein, G Geginat
1Institute of Medical Microbiology and Hygiene Mannheim, Faculty of Clinical Medicine, University of Heidelberg, 68167, Mannheim, Germany.
Abstract:
We compared the contribution of T cell memory to the clearance of the fungus Candida albicans from the liver, kidneys and brain of Balb/c mice in a model of secondary systemic infection. In secondary infection, the fungi were more rapidly eliminated from the liver and kidneys than during primary infection. This was most pronounced in the liver where the fungi were eliminated at day 14 of infection. In contrast, in the brain, cultivable yeasts were still detectable 35 days after infection. Although both CD4(+) and CD8(+) cells could be detected in the brain with immunohistology, these cells appeared later in infection and in lower numbers than in the liver, and there were no significant differences in the numbers of T cells detected in the brain between primary and secondary infection. In contrast to the liver and the kidneys where an effect of T cells on the fungal load could be demonstrated, depletion of neither CD4(+) nor CD8(+) nor Thy-1.2(+) cells resulted in a significant increase of the amount of fungi in the brain above levels measured in secondarily infected mice treated with irrelevant antibodies. We conclude that the contribution of CD4(+) and CD8(+) cells to the clearance of C. albicans in secondary infection is organ-dependent and that T cell memory is inefficient in the brain.
Insights
T cell memory aids Candida albicans clearance in secondary infections, particularly in the liver and kidneys. However, T cell memory is ineffective in clearing fungi from the brain.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Systemic Candida albicans infections pose significant health risks.
- T cell memory plays a crucial role in adaptive immunity against fungal pathogens.
- Understanding organ-specific immune responses is vital for effective treatment strategies.
Purpose of the Study:
- To compare the contribution of T cell memory to Candida albicans clearance in the liver, kidneys, and brain during secondary systemic infection.
- To investigate the organ-dependent efficacy of T cell memory in controlling fungal infections.
Main Methods:
- Utilized a murine model of secondary systemic Candida albicans infection.
- Employed immunohistology to detect CD4(+) and CD8(+) T cells in infected organs.
- Assessed fungal load and T cell populations in the liver, kidneys, and brain.
- Depleted specific T cell populations (CD4(+), CD8(+), Thy-1.2(+)) to evaluate their impact on fungal clearance.
Main Results:
- Secondary infection led to more rapid Candida albicans clearance from the liver and kidneys compared to primary infection.
- Fungi were cleared from the liver by day 14, but remained detectable in the brain up to 35 days post-infection.
- While CD4(+) and CD8(+) T cells were present in the brain, their numbers and timing differed from the liver, with no significant difference between primary and secondary infections.
- Depletion of T cells did not significantly increase fungal load in the brain during secondary infection.
Conclusions:
- The contribution of CD4(+) and CD8(+) T cells to Candida albicans clearance is organ-dependent during secondary systemic infection.
- T cell memory demonstrates inefficiency in clearing Candida albicans from the brain.