Longitudinal study of changes in γδT cells and CD4+ T cells upon asymptomatic malaria infection in Indonesian children
Longitudinal study of changes in γδT cells and CD4+ T cells upon asymptomatic malaria infection in Indonesian children
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DOI：
10.1038/s41598-017-09099-z
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发表时间：
2017-08-18
影响因子：
4.6
通讯作者：
Yazdanbakhsh, Maria
中科院分区：
文献类型：
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作者：
de Jong, Sanne E.;Asscher, Vera E. R.;Yazdanbakhsh, Maria
γ δ T细胞和CD 4 + T细胞都与疟疾的免疫有关，但它们与感染的自然获得或丧失的关系以前从未被研究过。因此，我们对生活在印度尼西亚疟疾流行区的无症状儿童进行了为期21个月的随访。γ δ T细胞的百分比与当前和以前的感染有关，感染儿童的百分比高于未感染儿童，并在感染消退后下降。与未感染儿童相比，感染儿童的Th 1和Th 17细胞水平也较高，CD 25 Hi FOXP 3+调节性T细胞（T细胞）水平较低，但Th 2细胞水平相似。然而，恶性疟原虫感染的红细胞（PfRBC）的TNF、IFN-γ和IL-17细胞因子反应相似，而感染儿童的IL-5和IL-13反应较低。此外，受感染的儿童具有更多表型耗尽的PD-1+ CD 4 + T细胞，更多表达TNF-RII的T细胞，以及对PfRBC的更高的IL-10应答，这些应答在感染消退后持续存在。总之，这项研究表明，无症状疟疾感染与循环先天性和适应性T细胞的频率和免疫调节的一些长期变化有关，这可能部分解释了疟疾预暴露如何影响对随后免疫挑战的反应。
Both gamma delta T cells and CD4+ T cells have been implicated in immunity to malaria, but their association with natural gain or loss of infection has not been studied before. Therefore, we followed up asymptomatic children living in an area endemic for malaria in Indonesia for 21 months. The percentage of gamma delta T cells was related to both current and previous infection, with higher percentages in infected than uninfected children and declining after infections resolve. Infected children also had higher levels of Th1 and Th17 cells, lower levels of CD25Hi FOXP3+ regulatory T cells (Tregs), but similar levels of Th2 cells as compared to uninfected children. However, TNF, IFN-gamma, and IL-17 cytokine responses to Plasmodium falciparuminfected red blood cells (PfRBCs) were similar, while IL-5 and IL-13 responses were lower in infected children. Furthermore, infected children had more phenotypically exhausted PD-1+ CD4+ T cells, more Tregs expressing TNF-RII, and higher IL-10 responses to PfRBCs, which persisted following resolution of infection. Altogether, this study demonstrates that asymptomatic malaria infection is associated with some long-lasting changes in the frequencies and immunoregulation of circulating innate and adaptive T cells, which might in part explain how pre-exposure to malaria affects responses to subsequent immunological challenges.