BACKGROUND Rhodesiense sleeping sickness is caused by infection with T. b rhodesiense parasites resulting in an acute disease that is fatal if not treated in time. The aim of this study was to understand the global impact of active T. b rhodesiense infection on the patient's immune response in the early and late stages of the disease. METHODS RNASeq was carried out on blood and cerebral spinal fluid (CSF) samples obtained from T. b. rhodesiense infected patients. The control samples used were from healthy individuals in the same foci. The Illumina sequenced reads were analysed using the Tuxedo suite pipeline (Tophat, Cufflinks, Cuffmerge, Cuffdiff) and differential expression analysis carried out using the R package DESeq2. The gene enrichment and function annotation analysis were done using the ToppCluster, DAVID and InnateDB algorithms. RESULTS We previously described the transcriptomes of T. b rhodesiense from infected early stage blood (n = 3) and late stage CSF (n = 3) samples from Eastern Uganda. We here identify human transcripts that were differentially expressed (padj < 0.05) in the early stage blood versus healthy controls (n = 3) and early stage blood versus late stage CSF. Differential expression in infected blood showed an enrichment of innate immune response genes whereas that of the CSF showed enrichment for anti-inflammatory and neuro-degeneration signalling pathways. We also identified genes (C1QC, MARCO, IGHD3-10) that were up-regulated (log2 FC > 2.5) in both the blood and CSF. CONCLUSION The data yields insights into the host's response to T. b rhodesiense parasites in the blood and central nervous system. We identified key pathways and signalling molecules for the predominant innate immune response in the early stage infection; and anti-inflammatory and neuro-degeneration pathways associated with sleep disorders in second stage infection. We further identified potential blood biomarkers that can be used for diagnosis of late stage disease without the need for lumbar puncture.

中文翻译：

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第二阶段人类非洲锥虫病的血液特征：转录组学方法。

背景技术罗得西亚昏睡病是由罗氏疟原虫的寄生虫感染引起的，导致急性疾病，如果不及时治疗会致命。这项研究的目的是了解在疾病的早期和晚期，活动性罗氏疟原虫感染对患者免疫反应的总体影响。方法对从T.b.获得的血液和脑脊髓液（CSF）样品进行RNASeq。罗得西亚州感染的患者。使用的对照样品来自相同病灶的健康个体。使用Tuxedo套件管道（Tophat，Cufflinks，Cuffmerge，Cuffdiff）分析Illumina测序的读段，并使用R软件包DESeq2进行差异表达分析。使用ToppCluster，DAVID和InnateDB算法进行基因富集和功能注释分析。结果我们先前描述了来自乌干达东部感染的早期血液（n = 3）和晚期脑脊液（n = 3）样本中的罗氏疟原虫的转录组。我们在这里鉴定出在早期血液与健康对照（n = 3）和早期血液与晚期CSF中差异表达（padj <0.05）的人类转录物。感染血液中的差异表达显示出先天免疫应答基因的丰富，而脑脊液中的表达却丰富了抗炎和神经退行性信号通路。我们还鉴定了在血液和脑脊液中均被上调（log2 FC> 2.5）的基因（C1QC，MARCO，IGHD3-10）。结论数据可洞察宿主对血液和中枢神经系统中罗氏疟原虫寄生虫的反应。我们确定了早期感染中主要的先天免疫应答的关键途径和信号分子。第二阶段感染中与睡眠障碍相关的抗炎和神经退行性途径。我们进一步确定了潜在的血液生物标记物，可用于诊断晚期疾病而无需穿刺腰椎。