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Published on: December 2, 2022
Elucidating the pathogenesis of spores from the human fungal pathogen Cryptococcus neoformans
Steven S Giles1, Taylor R T Dagenais, Michael R Botts
1Department of Biomolecular Chemistry, University of Wisconsin-Madison, USA.
Abstract:
Cryptococcus neoformans was first described as a human fungal pathogen more than a century ago. One aspect of the C. neoformans infectious life cycle that has been the subject of earnest debate is whether the spores are pathogenic. Despite much speculation, no direct evidence has been presented to resolve this outstanding question. We present evidence that C. neoformans spores are pathogenic in a mouse intranasal inhalation model of infection. In addition, we provide mechanistic insights into spore-host interactions. We found that C. neoformans spores were phagocytosed by alveolar macrophages via interactions between fungal beta-(1,3)-glucan and the host receptors Dectin-1 and CD11b. Moreover, we discovered an important link between spore survival and macrophage activation state: intracellular spores were susceptible to reactive oxygen-nitrogen species. We anticipate these results will serve as the basis for a model to further investigate the pathogenic implications of infections caused by fungal spores.
Insights
Cryptococcus neoformans spores are pathogenic, causing infection in mice. Spore survival depends on macrophage interactions and susceptibility to reactive oxygen-nitrogen species.
Area of Science:
- Mycology
- Infectious Diseases
- Immunology
Background:
- Cryptococcus neoformans is a fungal pathogen with an debated infectious life cycle.
- The pathogenic potential of C. neoformans spores remains unresolved due to lack of direct evidence.
Purpose of the Study:
- To investigate the pathogenicity of C. neoformans spores.
- To elucidate the mechanisms of spore-host interactions during infection.
Main Methods:
- A mouse intranasal inhalation model was used to study C. neoformans spore infection.
- Mechanistic insights into spore-macrophage interactions were explored.
Main Results:
- C. neoformans spores were demonstrated to be pathogenic in the mouse model.
- Spores were phagocytosed by alveolar macrophages through interactions involving beta-(1,3)-glucan and host receptors Dectin-1 and CD11b.
- Intracellular spore survival was linked to macrophage activation state and susceptibility to reactive oxygen-nitrogen species.
Conclusions:
- C. neoformans spores possess pathogenic potential.
- Spore-host interactions, particularly with macrophages, are crucial for fungal pathogenesis.
- Further research into fungal spore infections is warranted.
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