Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection
Characterization of T cell activation and regulation in children with asymptomatic Plasmodium falciparum infection
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DOI：
10.1186/s12936-018-2410-6
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发表时间：
2018-07-13
期刊：
影响因子：
3
通讯作者：
Ndifon, Wilfred
中科院分区：
文献类型：
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作者：
Frimpong, Augustina;Kusi, Kwadwo Asamoah;Ndifon, Wilfred
背景：无症状疟原虫感染的特点是没有临床疾病和限制寄生虫复制的能力。恶性疟原虫感染中调节性T细胞（Tregs）水平的升高与临床疾病的发生风险相关，这表明无症状感染者的Treg频率可能降低。然而，在无症状疟疾中Tregs、细胞活化和寄生虫控制之间的关系尚不清楚。方法：在一项横断面研究中，使用流式细胞术比较有症状、无症状和未感染儿童在感染红细胞裂解物（irbc）刺激前后的Tregs和其他T细胞活化表型水平。此外，还研究了这些T细胞表型与寄生虫血症之间的关系。结果：在无症状感染的儿童中，Tregs和活化T细胞的水平与健康对照组相当，但明显低于有症状的儿童。iRBC刺激后，无症状儿童的Tregs水平仍然低于有症状儿童。相比之下，无症状儿童的活化T细胞水平更高。引人注目的是，两种T细胞激活表型（CD8+CD69+和CD8+CD25+CD69+）的刺激前水平和两种调节性表型（CD4+CD25+Foxp3+和CD8+CD25+Foxp3+）的刺激后水平与寄生虫病的个体差异显著正相关，并解释了68%的个体差异。基于这四种表型水平的机器学习模型准确地区分了无症状和有症状的儿童（敏感性= 86%，特异性= 94%），表明这些表型控制着观察到的疾病状态变化。结论：与有症状的恶性疟原虫感染相比，儿童无症状感染的特点是Tregs和活化T细胞水平较低，这与较低的寄生虫血症有关。结果表明，在研究的撒哈拉以南非洲人口中，T细胞调节和激活表型控制着寄生虫血症和儿童疟疾的疾病状态。
Background: Asymptomatic Plasmodium infections are characterized by the absence of clinical disease and the ability to restrict parasite replication. Increasing levels of regulatory T cells (Tregs) in Plasmodium falciparum infections have been associated with the risk of developing clinical disease, suggesting that individuals with asymptomatic infections may have reduced Treg frequency. However, the relationship between Tregs, cellular activation and parasite control in asymptomatic malaria remains unclear.Methods: In a cross-sectional study, the levels of Tregs and other T cell activation phenotypes were compared using flow cytometry in symptomatic, asymptomatic and uninfected children before and after stimulation with infected red blood cell lysates (iRBCs). In addition, the association between these T cell phenotypes and parasitaemia were investigated.Results: In children with asymptomatic infections, levels of Tregs and activated T cells were comparable to those in healthy controls but significantly lower than those in symptomatic children. After iRBC stimulation, levels of Tregs remained lower for asymptomatic versus symptomatic children. In contrast, levels of activated T cells were higher for asymptomatic children. Strikingly, the pre-stimulation levels of two T cell activation phenotypes (CD8+CD69+ and CD8+CD25+CD69+) and the post-stimulation levels of two regulatory phenotypes (CD4+CD25+Foxp3+ and CD8+CD25+Foxp3+) were significantly positively correlated with and explained 68% of the individual variation in parasitaemia. A machine-learning model based on levels of these four phenotypes accurately distinguished between asymptomatic and symptomatic children (sensitivity= 86%, specificity= 94%), suggesting that these phenotypes govern the observed variation in disease status.Conclusion: Compared to symptomatic P falciparum infections, in children asymptomatic infections are characterized by lower levels of Tregs and activated T cells, which are associated with lower parasitaemia. The results indicate that T cell regulatory and activation phenotypes govern both parasitaemia and disease status in paediatric malaria in the studied sub-Saharan African population.