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

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.

摘要 新型隐球菌（Cryptococcus neoformans）与格特隐球菌（Cryptococcus gattii）是隐球菌病（cryptococcosis）的致病原，该疾病具有较高的致死率。此类疾病的发生发展依赖真菌细胞与巨噬细胞的相互作用，隐球菌可在巨噬细胞内定植并增殖。为解析隐球菌细胞调控巨噬细胞活性的分子机制，本研究对暴露于隐球菌属（Cryptococcus spp.）菌株的巨噬细胞进行了全基因组规模的转录变化比较分析。研究检测到，暴露于隐球菌细胞的巨噬细胞中近40个基因的表达发生改变。主要调控过程与mTOR通路相关，该通路相关基因在与隐球菌共孵育的巨噬细胞中表达量下调。此外，与真菌细胞共孵育的巨噬细胞中，p70S6K与GSK-3β的磷酸化水平同样降低。综上，隐球菌的存在可驱动巨噬细胞内mTOR通路的调控，这可能是为了提升病原体的存活能力。