BACKGROUND Transcriptional profiling of the human immune response to malaria has been used to identify diagnostic markers, understand the pathogenicity of severe disease and dissect the mechanisms of naturally acquired immunity (NAI). However, interpreting this body of work is difficult given considerable variation in study design, definition of disease, patient selection and methodology employed. This work details a comprehensive review of gene expression profiling (GEP) of the human immune response to malaria to determine how this technology has been applied to date, instances where this has advanced understanding of NAI and the extent of variability in methodology between studies to allow informed comparison of data and interpretation of results. METHODS Datasets from the gene expression omnibus (GEO) including the search terms; 'plasmodium' or 'malaria' or 'sporozoite' or 'merozoite' or 'gametocyte' and 'Homo sapiens' were identified and publications analysed. Datasets of gene expression changes in relation to malaria vaccines were excluded. RESULTS Twenty-three GEO datasets and 25 related publications were included in the final review. All datasets related to Plasmodium falciparum infection, except two that related to Plasmodium vivax infection. The majority of datasets included samples from individuals infected with malaria 'naturally' in the field (n = 13, 57%), however some related to controlled human malaria infection (CHMI) studies (n = 6, 26%), or cells stimulated with Plasmodium in vitro (n = 6, 26%). The majority of studies examined gene expression changes relating to the blood stage of the parasite. Significant heterogeneity between datasets was identified in terms of study design, sample type, platform used and method of analysis. Seven datasets specifically investigated transcriptional changes associated with NAI to malaria, with evidence supporting suppression of the innate pro-inflammatory response as an important mechanism for this in the majority of these studies. However, further interpretation of this body of work was limited by heterogeneity between studies and small sample sizes. CONCLUSIONS GEP in malaria is a potentially powerful tool, but to date studies have been hypothesis generating with small sample sizes and widely varying methodology. As CHMI studies are increasingly performed in endemic settings, there will be growing opportunity to use GEP to understand detailed time-course changes in host response and understand in greater detail the mechanisms of NAI.

中文翻译：

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利用基因表达研究来研究人类对疟疾感染的免疫反应。

背景技术人类对疟疾的免疫反应的转录谱已用于鉴定诊断标记，了解严重疾病的致病性并剖析自然获得性免疫（NAI）的机制。然而，鉴于研究设计，疾病定义，患者选择和所用方法的巨大差异，很难解释这一工作。这项工作详细介绍了人类对疟疾的免疫反应的基因表达谱（GEP）的全面综述，以确定该技术迄今的应用方式，在这种情况下，人们对NAI有了更深入的了解，并且研究之间的方法变异程度允许知情的数据比较和结果解释。方法来自基因表达综合（GEO）的数据集，包括搜索词；' 鉴定了疟原虫”或“疟疾”或“子孢子”或“裂殖子”或“配子体”和“智人”并分析了出版物。排除了与疟疾疫苗有关的基因表达变化的数据集。结果最终评价包括23个GEO数据集和25个相关出版物。除了两个与间日疟原虫感染有关的数据集以外，所有数据集都与恶性疟原虫感染有关。大多数数据集包括来自现场“自然”感染疟疾的个体的样本（n = 13、57％），但是一些数据与受控人类疟疾感染（CHMI）研究（n = 6、26％）或受刺激的细胞有关体外含疟原虫（n = 6，26％）。大多数研究检查了与寄生虫血液阶段有关的基因表达变化。根据研究设计，样本类型，使用的平台和分析方法，确定了数据集之间的显着异质性。七个数据集专门研究了与NAI相关的针对疟疾的转录变化，并有证据支持抑制先天性促炎反应是其中大多数研究的重要机制。但是，对这项工作的进一步解释受到研究与小样本量之间异质性的限制。结论疟疾中的GEP是一种潜在的有力工具，但是迄今为止，研究一直以小样本量和广泛变化的方法产生假说。随着CHMI研究越来越多地在地方性环境中进行，