Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting.
Dendritic cell responses to Plasmodium falciparum in a malaria-endemic setting.
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DOI：
10.1186/s12936-020-03533-w
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发表时间：
2021-01-06
期刊：
影响因子：
3
通讯作者：
Götz A
中科院分区：
文献类型：
--
作者：
Turner TC;Arama C;Ongoiba A;Doumbo S;Doumtabé D;Kayentao K;Skinner J;Li S;Traore B;Crompton PD;Götz A
恶性疟原虫是全世界大多数疟疾病例的原因，撒哈拉以南非洲的儿童是受影响最脆弱的群体。非无菌临床免疫保护症状发展缓慢，是相对短暂的。此外，目前的疟疾候选疫苗未能在流行环境中产生持久的高水平保护，这可能是由于疟疾寄生虫本身的免疫调节作用。由于树突状细胞在启动免疫反应中起着至关重要的作用，本研究的目的是更好地了解累积疟疾暴露以及并发恶性疟原虫感染对树突状细胞表型和功能的影响。在这项横断面研究中，评估了从具有终身疟疾暴露史的马里成年人的外周血样本中新鲜分离的树突状细胞的表型和功能，这些成年人未感染恶性疟原虫（n = 27）或无症状感染恶性疟原虫（n = 8）。此外，在这些成人和马里儿童（n = 19）与急性症状疟疾的血浆细胞因子和趋化因子水平进行了测量。除了在无症状感染的马里成年人中浆细胞样树突状细胞频率较低外，外周血树突状细胞亚群频率和HLA-DR表面表达在感染状态下没有差异。未感染的马里成年人的外周血髓样树突状细胞通过上调共刺激分子HLA-DR、CD 80、CD 86和CD 40并分泌IL-10、CXCL 9和CXCL 10对恶性疟原虫血液期寄生虫的体外刺激作出反应。相比之下，无症状感染的马里成年人的骨髓树突状细胞没有表现出显着的反应高于未感染的红细胞对照。IL-10和CXCL 9血浆水平在无症状成人和急性疟疾儿童中均升高。这项研究的结果表明，终身接触疟疾的未感染成年人的骨髓树突状细胞能够上调共刺激分子并产生细胞因子。疟疾暴露个体的mDCs是否是能够产生适当免疫应答的有效抗原呈递细胞仍有待确定。这些数据还强调了IL-10和CXCL 9是无症状和急性疟疾的重要因素，并增加了对疟疾流行地区无症状恶性疟原虫感染的理解。
Plasmodium falciparum causes the majority of malaria cases worldwide and children in sub-Saharan Africa are the most vulnerable group affected. Non-sterile clinical immunity that protects from symptoms develops slowly and is relatively short-lived. Moreover, current malaria vaccine candidates fail to induce durable high-level protection in endemic settings, possibly due to the immunomodulatory effects of the malaria parasite itself. Because dendritic cells play a crucial role in initiating immune responses, the aim of this study was to better understand the impact of cumulative malaria exposure as well as concurrent P. falciparum infection on dendritic cell phenotype and function. In this cross-sectional study, the phenotype and function of dendritic cells freshly isolated from peripheral blood samples of Malian adults with a lifelong history of malaria exposure who were either uninfected (n = 27) or asymptomatically infected with P. falciparum (n = 8) was assessed. Additionally, plasma cytokine and chemokine levels were measured in these adults and in Malian children (n = 19) with acute symptomatic malaria. With the exception of lower plasmacytoid dendritic cell frequencies in asymptomatically infected Malian adults, peripheral blood dendritic cell subset frequencies and HLA-DR surface expression did not differ by infection status. Peripheral blood myeloid dendritic cells of uninfected Malian adults responded to in vitro stimulation with P. falciparum blood-stage parasites by up-regulating the costimulatory molecules HLA-DR, CD80, CD86 and CD40 and secreting IL-10, CXCL9 and CXCL10. In contrast, myeloid dendritic cells of asymptomatically infected Malian adults exhibited no significant responses above the uninfected red blood cell control. IL-10 and CXCL9 plasma levels were elevated in both asymptomatic adults and children with acute malaria. The findings of this study indicate that myeloid dendritic cells of uninfected adults with a lifelong history of malaria exposure are able to up-regulate co-stimulatory molecules and produce cytokines. Whether mDCs of malaria-exposed individuals are efficient antigen-presenting cells capable of mounting an appropriate immune response remains to be determined. The data also highlights IL-10 and CXCL9 as important factors in both asymptomatic and acute malaria and add to the understanding of asymptomatic P. falciparum infections in malaria-endemic areas.
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影响因子：
15.8
作者：
Chen I;Clarke SE;Gosling R;Hamainza B;Killeen G;Magill A;O'Meara W;Price RN;Riley EM
通讯作者：
Riley EM
影响因子：
6.4
作者：
Collin M;Bigley V
通讯作者：
Bigley V
影响因子：
15.9
作者：
Crompton, Peter D.;Pierce, Susan K.;Miller, Louis H.
通讯作者：
Miller, Louis H.
影响因子：
4.4
作者：
Ioannidis, Lisa J.;Nie, Catherine Q.;Hansen, Diana S.
通讯作者：
Hansen, Diana S.
影响因子：
82.9
作者：
通讯作者：
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