Department of Dermatology, Southwest Hospital, Army Medical University, Chongqing, 400038, China.
Department of Dermatology, The Seventh Medical Center of PLA General Hospital, Beijing, 100700, China.
Mycopathologia. 2021 Jun;186(3):355-365. doi: 10.1007/s11046-021-00552-2. Epub 2021 Apr 20.
Trichosporon asahii (T. asahii) is a clinically important opportunistic pathogenic fungus capable of causing systemic lethal infection in immunosuppressive and immunodeficient hosts. However, the mechanism of the host immune response upon T. asahii infection has not been elucidated. Recent evidence has shown that long noncoding RNAs (lncRNAs) play key roles in regulating the immune response to resist microbial infections. In this study, we analyzed the expression profiles of lncRNAs at 12 and 24 h post-infection (hpi) in THP-1 cells infected with T. asahii using RNA sequencing (RNA-Seq). A total of 64 and 160 lncRNAs displayed significant differentially expressed (DE) at 12 h and 24 hpi, respectively. Among these lncRNAs, 18 lncRNAs were continuous DE at two time points. The DE of eight candidate lncRNAs were verified by real time quantitative polymerase chain reaction (RT-qPCR). Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to analyze the cis-target genes of 18 DE lncRNAs. The results showed that they were enriched in signaling pathways related to the host immune response, indicating that these lncRNAs might play important roles in fungi-host interactions. Finally, we explored the function of lncRNA NEAT1 and found that the expression of TNF-α and IL-1β declined after NEAT1 knockdown in T. asahii-infected THP-1 cells. To our knowledge, this is the first report of a expression analysis of lncRNAs in macrophages infected with T. asahii. Our study helps to elucidate the role of lncRNAs in the host immune response to early infection by T. asahii.
新生隐球菌(T. asahii)是一种重要的临床机会致病性真菌,能够在免疫抑制和免疫缺陷宿主中引起系统性致命感染。然而,宿主对 T. asahii 感染的免疫反应机制尚未阐明。最近的证据表明,长非编码 RNA(lncRNAs)在调节免疫反应以抵抗微生物感染方面发挥着关键作用。在这项研究中,我们使用 RNA 测序(RNA-Seq)分析了 T. asahii 感染 THP-1 细胞后 12 和 24 小时(hpi)的 lncRNA 表达谱。共有 64 和 160 个 lncRNA 在 12 h 和 24 hpi 时分别表现出显著差异表达(DE)。在这些 lncRNA 中,18 个 lncRNA 在两个时间点连续 DE。通过实时定量聚合酶链反应(RT-qPCR)验证了 8 个候选 lncRNA 的 DE。进行了基因本体和京都基因与基因组百科全书通路分析,以分析 18 个 DE lncRNA 的 cis 靶基因。结果表明,它们富集在与宿主免疫反应相关的信号通路中,表明这些 lncRNA 可能在真菌-宿主相互作用中发挥重要作用。最后,我们探索了 lncRNA NEAT1 的功能,发现 T. asahii 感染的 THP-1 细胞中 NEAT1 敲低后 TNF-α和 IL-1β 的表达下降。据我们所知,这是首次报道巨噬细胞感染 T. asahii 时 lncRNA 的表达分析。我们的研究有助于阐明 lncRNA 在宿主对 T. asahii 早期感染的免疫反应中的作用。