Plasmodium vivax but Not Plasmodium falciparum Blood-Stage Infection in Humans Is Associated with the Expansion of a CD8+ T Cell Population with Cytotoxic Potential.
Plasmodium vivax but Not Plasmodium falciparum Blood-Stage Infection in Humans Is Associated with the Expansion of a CD8+ T Cell Population with Cytotoxic Potential.
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DOI：
10.1371/journal.pntd.0005031
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发表时间：
2016-12
影响因子：
3.8
通讯作者：
Doolan DL
中科院分区：
文献类型：
--
作者：
Burel JG;Apte SH;McCarthy JS;Doolan DL
间日疟原虫和恶性疟原虫对宿主细胞表现出不同的嗜性，并诱导非常不同的临床症状和病理学，这表明保护所需的免疫应答在这两个物种之间可能不同。然而，没有研究定性地比较人类初次接触和感染后对恶性疟原虫或间日疟原虫的免疫反应。在这里，我们表明，这两个物种不同的细胞免疫反应引起的原发感染。具体地，间日疟原虫诱导表达活化标志物CD 38的CD 8 + T细胞亚群的扩增，而恶性疟原虫诱导CD 38 + CD 4 + T细胞的扩增。与CD 38-CD 8 + T细胞相比，并且与恶性疟原虫感染期间循环的CD 38 + CD 8 + T细胞相比，在间日疟原虫感染后扩增的CD 38 + CD 8 + T细胞群显示出更大的细胞毒性潜力。我们假设间日疟原虫感染导致更强的CD 38 + CD 8 + T细胞活化，因为其对表达MHC-I的网织红细胞的偏好性，与成熟红细胞不同，网织红细胞可以直接将抗原呈递给CD 8 + T细胞。这项研究提供了第一条证据，表明CD 8 + T细胞在间日疟原虫血液阶段免疫中的效应作用。这也是第一份关于原发性疟原虫感染后扩增的T细胞亚群中物种特异性差异的报告，表明疟疾疫苗的开发可能需要根据靶寄生虫进行优化。anzctr.org.au ACTRN 12612000814875; anzctr.org.au ACTRN 12613000565741; anzctr.org.au ACTRN 12613001040752; ClinicalTrials.gov NCT 02281344; anzctr.org.au ACTRN 12612001096842; anzctr.org.au ACTRN 12613001008718疟原虫感染后有助于人体保护性免疫的特异性免疫应答尚未得到充分表征。间日疟原虫和恶性疟原虫是大多数人类感染的病原体，但对间日疟原虫特异性免疫应答以及它们是否与恶性疟原虫相似或不同却知之甚少。在此，我们确定间日疟原虫和恶性疟原虫在初次感染后引起不同的细胞免疫应答，其中在间日疟原虫中具有细胞毒性潜力的CD 38 + CD 8 + T细胞亚群扩增，但在恶性疟原虫感染中不扩增。这项研究首次提供了间日疟原虫血液期感染中CD 8 + T细胞活化的证据，并证明了对疟疾的物种依赖性宿主免疫应答的存在。这些发现对间日疟原虫疫苗的开发具有重要意义，并建议未来的疟疾疫苗研究应根据靶疟原虫进行调整。
P. vivax and P. falciparum parasites display different tropism for host cells and induce very different clinical symptoms and pathology, suggesting that the immune responses required for protection may differ between these two species. However, no study has qualitatively compared the immune responses to P. falciparum or P. vivax in humans following primary exposure and infection. Here, we show that the two species differ in terms of the cellular immune responses elicited following primary infection. Specifically, P. vivax induced the expansion of a subset of CD8+ T cells expressing the activation marker CD38, whereas P. falciparum induced the expansion of CD38+ CD4+ T cells. The CD38+ CD8+ T cell population that expanded following P. vivax infection displayed greater cytotoxic potential compared to CD38- CD8+ T cells, and compared to CD38+ CD8+ T cells circulating during P. falciparum infection. We hypothesize that P. vivax infection leads to a stronger CD38+ CD8+ T cell activation because of its preferred tropism for MHC-I-expressing reticulocytes that, unlike mature red blood cells, can present antigen directly to CD8+ T cells. This study provides the first line of evidence to suggest an effector role for CD8+ T cells in P. vivax blood-stage immunity. It is also the first report of species-specific differences in the subset of T cells that are expanded following primary Plasmodium infection, suggesting that malaria vaccine development may require optimization according to the target parasite. anzctr.org.au ACTRN12612000814875; anzctr.org.au ACTRN12613000565741; anzctr.org.au ACTRN12613001040752; ClinicalTrials.gov NCT02281344; anzctr.org.au ACTRN12612001096842; anzctr.org.au ACTRN12613001008718 The specific immune responses that contribute to protective immunity in humans following Plasmodium infection are yet to be fully characterized. The species P. vivax and P. falciparum account for most human infections, yet little is known about P. vivax specific immune responses and whether they are similar to or distinct from P. falciparum. Here, we establish that P. vivax and P. falciparum elicit distinct cellular immune responses following primary infection, with the expansion of a subset of CD38+ CD8+ T cells with a cytotoxic potential in P. vivax but not in P. falciparum infection. This study provides the first evidence for the activation of CD8+ T cells in P. vivax blood-stage infection and demonstrates the existence of species-dependent host immune responses to malaria. These findings have important implications for P. vivax vaccine development, and suggest that future malaria vaccine studies should be adapted according to the target Plasmodium spp.
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影响因子：
4.6
作者：
Imai T;Ishida H;Suzue K;Hirai M;Taniguchi T;Okada H;Suzuki T;Shimokawa C;Hisaeda H
通讯作者：
Hisaeda H
影响因子：
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影响因子：
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作者：
Burel JG;Apte SH;Groves PL;Klein K;McCarthy JS;Doolan DL
通讯作者：
Doolan DL
影响因子：
3
作者：
Rockett RJ;Tozer SJ;Peatey C;Bialasiewicz S;Whiley DM;Nissen MD;Trenholme K;Mc Carthy JS;Sloots TP
通讯作者：
Sloots TP
影响因子：
8.8
作者：
Horne-Debets, Joshua M.;Faleiro, Rebecca;Wykes, Michelle N.
通讯作者：
Wykes, Michelle N.