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Size Matters: Measurement of Capsule Diameter in Cryptococcus neoformans
Published on: February 27, 2018
Complementation of a capsule deficient Cryptococcus neoformans with CAP64 restores virulence in a murine lung
Julie A Wilder1, Gwyneth K Olson, Yun C Chang
1University of New Mexico School of Medicine, Department of Pathology, Albuquerque, New Mexico 87131-5301, USA.
Abstract:
Cryptococcosis is a systemic infection in humans caused by the opportunistic fungal pathogen, Cryptococcus neoformans. The infection usually presents as chronic meningoencephalitis, but infects via the respiratory tract. A polysaccharide capsule is a major virulence factor, which allows the yeast to resist host defenses. However, the essential role of the capsule in allowing it to resist host defenses during the initial lung infection has not been clearly shown. A mutant acapsular C. neoformans strain 602 was complemented with the CAP64 gene to obtain an encapsulated strain, TYCC38-602. TYCC38-602 persisted in the lungs of C.B-17 mice after intratracheal inoculation and disseminated to the brain, whereas the mutant acapsular 602 and the plasmid control transformant CIP3-602 strains grew less readily in the lung and were infrequently detected in the brain. T cell-mediated immunity, developed to the encapsulated organism, was required to control growth within the lungs and had a significant impact on numbers of yeasts detected in the brain. The parent acapsular strain, but not the transformant control, also required T cells for optimal inhibition of growth within the lung, but not for maintaining control of the colony-forming units (cfu) in the brain. In summary, the cryptococcal capsule plays an important role in lung virulence and dissemination to the brain, and intact immunity is required to control lung growth of the encapsulated yeast.
Insights
The cryptococcal capsule is crucial for virulence in lung infections and brain dissemination. Intact T cell immunity is essential for controlling encapsulated Cryptococcus neoformans in the lungs.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Cryptococcosis is a serious systemic infection caused by Cryptococcus neoformans.
- The fungal polysaccharide capsule is a key virulence factor, but its role in initial lung infection requires further study.
- Understanding capsule function is vital for developing effective treatments against cryptococcal infections.
Purpose of the Study:
- To investigate the essential role of the Cryptococcus neoformans capsule in lung virulence and dissemination to the brain.
- To determine the impact of T cell-mediated immunity on controlling cryptococcal infection in the lungs and brain.
Main Methods:
- Generation of an encapsulated Cryptococcus neoformans strain (TYCC38-602) by complementing an acapsular mutant (602) with the CAP64 gene.
- Intratracheal inoculation of C.B-17 mice with encapsulated, acapsular, and control strains.
- Assessment of fungal burden in lungs and brains, and evaluation of T cell-mediated immunity.
Main Results:
- The encapsulated strain TYCC38-602 persisted in the lungs and disseminated to the brain, unlike the acapsular strain 602.
- T cell-mediated immunity was required to control fungal growth in the lungs and significantly impacted yeast numbers in the brain.
- The acapsular strain also required T cells for optimal lung growth inhibition, but not for brain control.
Conclusions:
- The cryptococcal capsule plays a significant role in lung virulence and subsequent dissemination to the brain.
- Robust T cell-mediated immunity is essential for controlling the growth of encapsulated Cryptococcus neoformans within the lungs.

