Transcriptomic analysis reveals that mTOR pathway can be modulated in macrophage cells by the presence of cryptococcal cells

转录组分析表明,隐球菌细胞的存在可以调节巨噬细胞中的 mTOR 通路

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作者:Alícia C Piffer, Francine M Dos Santos, Marcos P Thomé, Camila Diehl, Ane Wichine Acosta Garcia, Uriel Perin Kinskovski, Rafael de Oliveira Schneider, Alexandra Gerber, Bruno César Feltes, Augusto Schrank, Ana Tereza R Vasconcelos, Guido Lenz, Lívia Kmetzsch, Marilene H Vainstein, Charley C Staats

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.

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