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Updated: Oct 25, 2025

Macrophage Cholesterol Depletion and Its Effect on the Phagocytosis of Cryptococcus neoformans
Published on: December 19, 2014
Transcriptomic analysis reveals that mTOR pathway can be modulated in macrophage cells by the presence of
Alícia C Piffer1, Francine M Dos Santos1, Marcos P Thomé1
1Universidade Federal do Rio Grande do Sul, Programa de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, Porto Alegre, RS, Brazil.
Abstract:
Cryptococcus neoformans and Cryptococcus gattii are the etiological agents of cryptococcosis, a high mortality disease. The development of such disease depends on the interaction of fungal cells with macrophages, in which they can reside and replicate. In order to dissect the molecular mechanisms by which cryptococcal cells modulate the activity of macrophages, a genome-scale comparative analysis of transcriptional changes in macrophages exposed to Cryptococcus spp. was conducted. Altered expression of nearly 40 genes was detected in macrophages exposed to cryptococcal cells. The major processes were associated with the mTOR pathway, whose associated genes exhibited decreased expression in macrophages incubated with cryptococcal cells. Phosphorylation of p70S6K and GSK-3β was also decreased in macrophages incubated with fungal cells. In this way, Cryptococci presence could drive the modulation of mTOR pathway in macrophages possibly to increase the survival of the pathogen.
Insights
Cryptococcus fungi manipulate macrophage activity by altering gene expression, specifically downregulating the mTOR pathway. This fungal manipulation may enhance pathogen survival during cryptococcosis infection.
Area of Science:
- Mycology
- Immunology
- Molecular Biology
Background:
- Cryptococcus neoformans and Cryptococcus gattii cause cryptococcosis, a severe infectious disease.
- Fungal pathogens reside and replicate within macrophages, crucial immune cells.
- Understanding host-pathogen interactions is key to combating cryptococcosis.
Purpose of the Study:
- To investigate the molecular mechanisms by which Cryptococcus spp. modulate macrophage activity.
- To perform a genome-scale analysis of transcriptional changes in macrophages upon Cryptococcus exposure.
Main Methods:
- Comparative genomic analysis of transcriptional changes in macrophages.
- Exposure of macrophages to Cryptococcus spp. fungal cells.
- Gene expression profiling and protein phosphorylation analysis.
Main Results:
- Nearly 40 genes showed altered expression in macrophages exposed to Cryptococcus.
- Genes associated with the mTOR pathway exhibited decreased expression.
- Decreased phosphorylation of p70S6K and GSK-3β was observed in infected macrophages.
Conclusions:
- Cryptococcus modulates the host macrophage mTOR pathway.
- This modulation potentially enhances fungal survival within macrophages.
- Targeting the mTOR pathway could be a therapeutic strategy against cryptococcosis.
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