Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-Universität Marburg, Marburg, Germany.
Institute for Lung Research, Universities of Giessen and Marburg Lung Center, Philipps-Universität Marburg, Marburg, Germany; Department of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Germany.
Life Sci. 2021 Apr 1;270:119158. doi: 10.1016/j.lfs.2021.119158. Epub 2021 Feb 2.
Malaria is a serious health threat in tropical countries. The causative parasite of Malaria tropica, the severe form, is the protozoan Plasmodium falciparum. In humans, it infects red blood cells, compromising blood flow and tissue perfusion. This study aims to identify potential biomarkers and RNA networks in leukocyte transcriptomes from patients suffering from Malaria tropica.
We identified differentially regulated mRNAs and microRNAs in peripheral blood leukocytes of healthy donors and Malaria patients. Genes whose expression changes were not attributable to changes in leukocyte composition were used for bioinformatics analysis and network construction. Using a previously published cohort of community-acquired pneumonia (CAP) patients, we established discriminating transcriptomic features versus Malaria. We aimed to establish differences between the patient groups by principal component (PCA) and receiving operator characteristic (ROC) analyses and in silico cell type deconvolution.
We found 870 genes that were significantly differentially expressed between healthy donors and Malaria patients. E2F1, BIRC5 and CCNB1 were identified to be primarily responsible for PCA separation of these two groups. We searched for biological function and found that cell cycle processes were strongly activated. By in silico cell type deconvolution, we attribute this to an expansion of γδ T cells. Additional discrimination between CAP and Malaria yielded 445 differentially expressed genes, among which immune proteasome transcripts PSMB8, PSMB9 and PSMB10 were significantly induced in Malaria.
We identified transcripts from patient leukocytes that differentiate between healthy, Malaria and CAP, and indicate a biological context with potential pathophysiological relevance.
疟疾是热带国家的严重健康威胁。恶性疟原虫是热带疟疾的病原体，是一种原生动物。在人类中，它感染红细胞，损害血液流动和组织灌注。本研究旨在鉴定来自患有热带疟疾的患者的白细胞转录组中的潜在生物标志物和 RNA 网络。
我们鉴定了健康供体和疟疾患者外周血白细胞中差异调节的 mRNA 和 microRNA。将表达变化归因于白细胞组成变化的基因用于生物信息学分析和网络构建。使用先前发表的社区获得性肺炎 (CAP) 患者队列，我们建立了区分疟疾的转录组特征。我们旨在通过主成分 (PCA) 和接受者操作特征 (ROC) 分析以及计算机细胞类型去卷积来建立患者组之间的差异。
我们发现 870 个基因在健康供体和疟疾患者之间的表达差异显著。E2F1、BIRC5 和 CCNB1 被确定为 PCA 分离这两组的主要原因。我们寻找生物学功能并发现细胞周期过程被强烈激活。通过计算机细胞类型去卷积，我们将其归因于 γδ T 细胞的扩增。CAP 和疟疾之间的额外区分产生了 445 个差异表达基因，其中免疫蛋白酶体转录物 PSMB8、PSMB9 和 PSMB10 在疟疾中显著诱导。
我们从患者白细胞中鉴定出区分健康、疟疾和 CAP 的转录本，并表明具有潜在病理生理相关性的生物学背景。
