Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States.
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, United States.
Front Immunol. 2023 Jul 3;14:1179314. doi: 10.3389/fimmu.2023.1179314. eCollection 2023.
Host gene and protein expression impact susceptibility to clinical malaria, but the balance of immune cell populations, cytokines and genes that contributes to protection, remains incompletely understood. Little is known about the determinants of host susceptibility to clinical malaria at a time when acquired immunity is developing.
We analyzed peripheral blood mononuclear cells (PBMCs) collected from children who differed in susceptibility to clinical malaria, all from a small town in Mali. PBMCs were collected from children aged 4-6 years at the start, peak and end of the malaria season. We characterized the immune cell composition and cytokine secretion for a subset of 20 children per timepoint (10 children with no symptomatic malaria age-matched to 10 children with >2 symptomatic malarial illnesses), and gene expression patterns for six children (three per cohort) per timepoint.
We observed differences between the two groups of children in the expression of genes related to cell death and inflammation; in particular, inflammatory genes such as CXCL10 and STAT1 and apoptotic genes such as XAF1 were upregulated in susceptible children before the transmission season began. We also noted higher frequency of HLA-DR+ CD4 T cells in protected children during the peak of the malaria season and comparable levels cytokine secretion after stimulation with malaria schizonts across all three time points.
This study highlights the importance of baseline immune signatures in determining disease outcome. Our data suggests that differences in apoptotic and inflammatory gene expression patterns can serve as predictive markers of susceptibility to clinical malaria.
宿主基因和蛋白质表达影响临床疟疾的易感性，但对于有助于保护的免疫细胞群体、细胞因子和基因的平衡仍不完全了解。在获得性免疫正在发展的情况下，人们对宿主易患临床疟疾的决定因素知之甚少。
我们分析了来自马里一个小镇的不同临床疟疾易感性儿童的外周血单核细胞（PBMC）。在疟疾季节开始、高峰和结束时，从 4-6 岁的儿童中收集 PBMC。我们对每个时间点的 20 名儿童中的一部分（与 10 名无症状疟疾年龄匹配的 10 名有>2 次症状性疟疾的儿童）进行免疫细胞组成和细胞因子分泌特征分析，并对每个时间点的 6 名儿童（每队列 3 名）进行基因表达模式分析。
我们观察到两组儿童在与细胞死亡和炎症相关的基因表达上存在差异；特别是，在疟疾传播季节开始前，易感性儿童的 CXCL10 和 STAT1 等炎症基因和 XAF1 等凋亡基因上调。我们还注意到，在疟疾季节高峰期，保护性儿童 HLA-DR+CD4 T 细胞的频率更高，在所有三个时间点用疟原虫裂殖体刺激后细胞因子分泌水平相当。
这项研究强调了基线免疫特征在决定疾病结局中的重要性。我们的数据表明，凋亡和炎症基因表达模式的差异可以作为临床疟疾易感性的预测标志物。
