Using a well-designed longitudinal cohort, we aimed to identify cytokines that were protective against malaria and to explore how they were influenced by genetic and immunological factors. 349 Mozambican pregnant women and their newborn babies were recruited and followed up for malaria outcomes until 24 months of age. Six Th1 cytokines in cord blood were screened for correlation with malaria incidence, of which IL-12 was selected for further analyses. We genotyped IL-12 polymorphisms in children/mothers and evaluated the genotype-phenotype associations and genetic effects on IL-12 levels. Maternal IL-12 concentrations were also investigated in relation to Plasmodium infections and cord blood IL-12 levels. Our data showed that high background IL-12 levels were prospectively associated with a low incidence of clinical malaria, while IL-12 production after parasite stimulation had the opposite effect on malaria incidence. IL-12 genotypes (IL-12b rs2288831/rs17860508) and the haplotype CGTTAGAG distribution were related to malaria susceptibility and background IL-12 levels. Maternal genotypes also exhibited an evident impact on host genotype-phenotype associations. Finally, a positive correlation in background IL-12 levels between maternal and cord blood was identified. Thus, cord blood background IL-12 concentrations are important for protecting children from clinical malaria, likely mediated by both genotypes (children&mothers) and maternal immunity.

中文翻译：

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脐带血IL-12可以在儿童早期阶段为临床疟疾提供保护。

我们使用设计合理的纵向队列研究，旨在确定对疟疾具有保护作用的细胞因子，并探讨它们如何受到遗传和免疫因素的影响。招募了349名莫桑比克孕妇及其新生婴儿，并对疟疾结果进行了随访，直到24个月大为止。筛选了脐带血中的6种Th1细胞因子与疟疾发病率的相关性，其中选择了IL-12进行进一步分析。我们对儿童/母亲的IL-12多态性进行基因分型，并评估了基因型与表型的关联以及遗传对IL-12水平的影响。还研究了孕妇血浆IL-12的浓度与疟原虫感染和脐血IL-12水平的关系。我们的数据表明，高背景IL-12水平与临床疟疾发生率低相关，寄生虫刺激后产生IL-12对疟疾发病率具有相反的影响。IL-12基因型（IL-12b rs2288831 / rs17860508）和单倍型CGTTAGAG分布与疟疾易感性和背景IL-12水平有关。孕产妇基因型也表现出对宿主基因型-表型关联的明显影响。最后，鉴定出母体和脐带血之间的背景IL-12水平呈正相关。因此，脐带血本底IL-12浓度对于保护儿童免受临床疟疾很重要，这可能是由基因型（儿童和母亲）和母体免疫介导的。IL-12基因型（IL-12b rs2288831 / rs17860508）和单倍型CGTTAGAG分布与疟疾易感性和背景IL-12水平有关。孕产妇基因型也表现出对宿主基因型-表型关联的明显影响。最后，鉴定出母体和脐带血之间的背景IL-12水平呈正相关。因此，脐带血本底IL-12浓度对于保护儿童免受临床疟疾很重要，这可能是由基因型（儿童和母亲）和母体免疫介导的。IL-12基因型（IL-12b rs2288831 / rs17860508）和单倍型CGTTAGAG分布与疟疾易感性和背景IL-12水平有关。孕产妇基因型也表现出对宿主基因型-表型关联的明显影响。最后，鉴定出母体和脐带血之间的背景IL-12水平呈正相关。因此，脐带血本底IL-12浓度对于保护儿童免受临床疟疾很重要，这可能是由基因型（儿童和母亲）和母体免疫介导的。