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Updated: Jul 4, 2026
07:32
Biolistic Transformation of a Fluorescent Tagged Gene into the Opportunistic Fungal Pathogen Cryptococcus neoformans
Published on: March 19, 2015
Phenotypic switching in Cryptococcus neoformans contributes to virulence by changing the immunological host response
Abraham Guerrero1, Bettina C Fries
1Departments of Microbiology and Immunology, Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Infection and Immunity
|July 2, 2008
Summary
The mucoid (MC) variant of Cryptococcus neoformans causes a severe inflammatory response in hosts lacking interleukin-10 (IL-10), negatively impacting survival. This suggests IL-10 is crucial for managing MC infections in Th1-polarized environments.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Cryptococcus neoformans exhibits phenotypic switching from smooth (SM) to more virulent mucoid (MC) colonies.
- Host responses differ between SM and MC variants, with lower IL-10 in MC infections.
- Interleukin-10 (IL-10) plays a differential role in SM versus MC infections.
Purpose of the Study:
- To compare survival rates and host responses in IL-10-depleted mice infected with SM or MC variants.
- To characterize the immune response in IL-10(-/-) mice, known for Th1 polarization and resistance.
Main Methods:
- Infection of IL-10-depleted (IL-10(-/-)) and wild-type mice with SM and MC variants of Cryptococcus neoformans.
- Comparison of survival rates and analysis of inflammatory cell recruitment (macrophages, NK, CD4, CD8 cells).
- Measurement of lung tissue cytokine levels (IL-21, IL-6, IL-4, TGF-β, IL-12, IFN-γ, TNF-α).
Main Results:
- IL-10(-/-) mice showed increased survival with SM infection but no benefit with MC infection compared to wild-type.
- MC infection induced a more pronounced Th1-polarized inflammatory response with greater immune cell recruitment in IL-10(-/-) mice.
- Elevated levels of multiple cytokines (IL-21, IL-6, IL-4, TGF-β, IL-12, IFN-γ) were observed in MC-infected mice, while TNF-α was higher in SM-infected IL-10(-/-) mice.
Conclusions:
- The MC variant triggers an excessive inflammatory response in a Th1-polarized host environment.
- The absence of IL-10 exacerbates the negative outcome of MC infections due to uncontrolled inflammation.
- IL-10 is critical for modulating host defense and ensuring better outcomes during Cryptococcus neoformans MC variant infections.
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