Abstract

Background

Although Schistosoma haematobium infection has been reported to be associated with alterations in immune function, in particular immune hyporesponsiveness, there have been only few studies that have used the approach of removing infection by drug treatment to establish this and to understand the underlying molecular mechanisms.

Methods

Schistosoma haematobium-infected schoolchildren were studied before and after praziquantel treatment and compared with uninfected controls. Cellular responses were characterized by cytokine production and flow cytometry, and in a subset of children RNA sequencing (RNA-Seq) transcriptome profiling was performed.

Results

Removal of S haematobium infection resulted in increased schistosome-specific cytokine responses that were negatively associated with CD4+CD25+FOXP3+ T-cells and accompanied by increased frequency of effector memory T-cells. Innate responses to Toll like receptor (TLR) ligation decreased with treatment and showed positive association with CD4⁺CD25⁺FOXP3⁺ T-cells. At the transcriptome level, schistosome infection was associated with enrichment in cell adhesion, whereas parasite removal was associated with a more quiescent profile. Further analysis indicated that alteration in cellular energy metabolism was associated with S haematobium infection and that the early growth response genes 2 and 3 (EGR 2 and EGR3), transcription factors that negatively regulate T-cell activation, may play a role in adaptive immune hyporesponsiveness.

Conclusions

Using a longitudinal study design, we found contrasting effects of schistosome infection on innate and adaptive immune responses. Whereas the innate immune system appears more activated, the adaptive immunity is in a hyporesponsive state reflected in alterations in CD4⁺CD25⁺FOXP3⁺ T-cells, cellular metabolism, and transcription factors involved in anergy.

中文翻译：

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对血吸虫血吸虫感染的加蓬小学生的免疫和转录组谱进行吡喹酮治疗的研究。

抽象的

背景

尽管据报道血吸虫血吸虫感染与免疫功能改变有关，尤其是免疫反应低下，但只有很少的研究使用药物治疗消除感染的方法来确定这种情况并了解其潜在的分子机制。

方法

在吡喹酮治疗前后对血吸虫血吸虫感染的学童进行了研究，并与未感染的对照组进行了比较。细胞反应的特征在于细胞因子的产生和流式细胞仪，并在儿童的一个子集中进行了RNA测序（RNA-Seq）转录组分析。

结果

去除沙门氏菌感染导致血吸虫特异性细胞因子应答增加，其与CD4 + CD25 + FOXP3 + T细胞负相关，并伴有效应记忆T细胞频率增加。对Toll样受体（TLR）结扎的先天反应随治疗而降低，并显示与CD4 ⁺ CD25 ⁺ FOXP3 ⁺ T细胞正相关。在转录组水平上，血吸虫感染与细胞粘附的丰富相关，而寄生虫清除与更静态的相关。进一步的分析表明，细胞能量代谢的改变与沙门氏菌有关 感染和早期生长反应基因2和3（EGR 2和EGR3），负调控T细胞活化的转录因子，可能在适应性免疫低反应性中起作用。

结论

使用纵向研究设计，我们发现血吸虫感染对先天性和适应性免疫反应的反作用。先天性免疫系统似乎被激活，而适应性免疫则处于低反应状态，这反映在CD4 ⁺ CD25 ⁺ FOXP3 ⁺ T细胞，细胞代谢和涉及无能的转录因子的改变中。