The effect of declining exposure on T cell-mediated immunity to Plasmodium falciparum - an epidemiological "natural experiment".
The effect of declining exposure on T cell-mediated immunity to Plasmodium falciparum - an epidemiological "natural experiment".
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DOI：
10.1186/s12916-016-0683-6
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发表时间：
2016-09-22
期刊：
影响因子：
9.3
通讯作者：
Ndungu FM
中科院分区：
文献类型：
--
作者：
Bediako Y;Ngoi JM;Nyangweso G;Wambua J;Opiyo M;Nduati EW;Bejon P;Marsh K;Ndungu FM
由于缺乏接触，自然获得的疟疾免疫力可能会丧失。最近在非洲部分地区传播的异质性减少意味着以前受到保护的大量人口可能会失去免疫力，同时仍有感染的风险。利用两个种族相似的长期队列儿童，他们历史上接触恶性疟原虫的水平相似，现在经历了非常不同的暴露水平，我们评估了寄生虫暴露减少对抗疟疾免疫的影响。用恶性疟原虫刺激每个队列儿童的外周血单个核细胞(PBMC)，比较它们对恶性疟原虫特异性增殖反应和细胞因子的反应。我们证明，虽然恶性疟原虫特异的CD4+T细胞在没有暴露的情况下保持不变，但这些细胞的增殖能力发生了很大的变化。从以前接触过恶性疟原虫的儿童中分离出来的、但现在生活在最低暴露区域(历史上接触过的)的儿童身上分离出来的CD4+T细胞，在刺激下的增殖明显高于从持续暴露于这种寄生虫的儿童中分离出来的细胞。同样，在恶性疟原虫刺激下，来自既往暴露儿童的PBMC表达较高水平的促炎细胞因子和较低水平的抗炎细胞因子。值得注意的是，我们发现自上次发热以来的持续时间与恶性疟原虫特异的CD4+T细胞增殖之间存在显著的正相关，而最近的发热发作与低增殖相关。在现有知识的背景下考虑，这些数据提出了一个模型，解释了在没有持续接触恶性疟原虫的情况下免疫力是如何丧失的。本文的在线版本(doi：10.1186/s12916-0160683-6)包含补充材料，授权用户可以使用。
Naturally acquired immunity to malaria may be lost with lack of exposure. Recent heterogeneous reductions in transmission in parts of Africa mean that large populations of previously protected people may lose their immunity while remaining at risk of infection. Using two ethnically similar long-term cohorts of children with historically similar levels of exposure to Plasmodium falciparum who now experience very different levels of exposure, we assessed the effect of decreased parasite exposure on antimalarial immunity. Peripheral blood mononuclear cells (PBMCs) from children in each cohort were stimulated with P. falciparum and their P. falciparum-specific proliferative and cytokine responses were compared. We demonstrate that, while P. falciparum-specific CD4+ T cells are maintained in the absence of exposure, the proliferative capacity of these cells is altered considerably. P. falciparum-specific CD4+ T cells isolated from children previously exposed, but now living in an area of minimal exposure (“historically exposed”) proliferate significantly more upon stimulation than cells isolated from children continually exposed to the parasite. Similarly, PBMCs from historically exposed children expressed higher levels of pro-inflammatory cytokines and lower levels of anti-inflammatory cytokines after stimulation with P. falciparum. Notably, we found a significant positive association between duration since last febrile episode and P. falciparum-specific CD4+ T cell proliferation, with more recent febrile episodes associated with lower proliferation. Considered in the context of existing knowledge, these data suggest a model explaining how immunity is lost in absence of continuing exposure to P. falciparum. The online version of this article (doi:10.1186/s12916-016-0683-6) contains supplementary material, which is available to authorized users.
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影响因子：
30.5
作者：
Butler, Noah S.;Moebius, Jacqueline;Pewe, Lecia L.;Traore, Boubacar;Doumbo, Ogobara K.;Tygrett, Lorraine T.;Waldschmidt, Thomas J.;Crompton, Peter D.;Harty, John T.
通讯作者：
Harty, John T.
DOI：
10.1073/pnas.0902745106
发表时间：
2009-04-28
影响因子：
11.1
作者：
Ben-Sasson, Shlomo Z.;Hu-Li, Jane;Paul, William E.
通讯作者：
Paul, William E.
影响因子：
3.1
作者：
Li, C;Corraliza, I;Langhorne, J
通讯作者：
Langhorne, J
影响因子：
2.2
作者：
Marsh, K;Kinyanjui, S
通讯作者：
Kinyanjui, S
影响因子：
4.4
作者：
Bejon, Philip;Mwacharo, Jedidah;Hill, Adrian V. S.
通讯作者：
Hill, Adrian V. S.