Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age.
Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age.
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恶性疟原虫感染了六岁以下的儿童，细胞因子相关的中性粒细胞外陷阱和抗核抗体。
DOI：
10.1186/1475-2875-7-41
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发表时间：
2008-02-29
期刊：
影响因子：
3
通讯作者：
Keller, Thomas Cs
中科院分区：
文献类型：
--
作者：
Baker, Virginia S.;Imade, Godwin E.;Molta, Norman B.;Tawde, Pallavi;Pam, Sunday D.;Obadofin, Michael O.;Sagay, Soloman A.;Egah, Daniel Z.;Iya, Daniel;Afolabi, Bangmboye B.;Baker, Murray;Ford, Karen;Ford, Robert;Roux, Kenneth H.;Keller, Thomas Cs
在感染恶性疟原虫的儿童中，血细胞组织病理学、血浆成分、免疫能力发展和疾病严重程度之间的关系仍然知之甚少。对患有单纯性疟疾的尼日利亚儿童的血液进行了分析，以深入了解这些关系。这项研究提供了循环中性粒细胞胞外陷阱 (NET) 和抗核 IgG 抗体 (ANA) 的证据。双链 DNA 中的 NET 和 ANA 以及细胞因子谱的存在表明，自身免疫机制可能在儿童中产生发病机制，但在成人中产生免疫保护作用。对 21 名六岁以下尼日利亚儿童的外周血涂片和血液样本进行了分析，这些儿童在开始磺胺多辛-乙胺嘧啶 (SP) 治疗前和治疗后 7 天出现无并发症的疟疾。载玻片用 Giemsa 和 DAPI 染色。通过免疫测定法测定促炎细胞因子 IFN-γ、IL-2、TNF、CRP 和 IL-6，选择抗炎细胞因子 TGF-β 和 IL-10 以及 ANA 的水平。这些儿童表现出循环 NET，其中有粘附的寄生虫和红细胞、ANA 水平升高、Th2 主导的细胞因子谱以及白细胞分类计数左移。在治疗前 86% 的儿童和 SP 治疗后 7 天的 100% 儿童中，非特异性 ANA 水平显着，但在寄生虫低传播季节收集的年龄匹配对照样本中，只有 33% 的非特异性 ANA 水平显着。 81% 的儿童在治疗前和治疗后的 ANA 特异性水平都很显着。这项研究的结果表明，NET 的形成和 dsDNA 的 ANA 可能会在感染恶性疟原虫的儿童中诱发病理，但会在成人中激活针对恶性疟疾的保护机制。讨论了 NET 和 dsDNA ANA 中体内循环染色质作为基于 CpG 寡核苷酸的疟疾疫苗反应低下的致病因素的重要性。
In Plasmodium falciparum-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults. Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP) treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-β and IL-10, and ANA were determined by immunoassay. The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment, but in only 33% of age-matched control samples collected during the season of low parasite transmission. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment. The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative factor in the hyporesponsiveness of CpG oligonucleotide-based malaria vaccines is discussed.
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