Discipline of Paediatrics, School of Medicine, Trinity College Dublin, the University of Dublin, Dublin, Ireland.
Trinity Research in Childhood Centre (TRiCC), Trinity College Dublin, the University of Dublin, Dublin, Ireland.
Pediatr Res. 2024 May;95(6):1611-1616. doi: 10.1038/s41390-024-03023-8. Epub 2024 Jan 17.
Infections cause significant morbidity and mortality in children with Severe Neurological Impairment (SNI). Alterations in immune cell numbers and function in children with neurodisability have been reported. We aimed to characterise neutrophil, monocyte and lymphocyte proportions and activation, at baseline and in response to stimulation with lipopolysaccharide, in children with SNI compared to healthy controls.
Whole blood samples of children with SNI and controls were incubated in the presence or absence of lipopolysaccharide (10 ng/ml). Monocyte and neutrophil function (Cluster of Differentiation (CD)11b, (TLR)-4 and CD66b expression) and lymphocytes were assessed by flow cytometry. Expression of genes involved in the inflammasome (NLR Family Pyrin Domain Containing(NLRP)-3, Apoptosis-Associated Speck-like protein (ASC) and Interleukin(IL)1β) were assessed by PCR.
Monocytes and CD8+ T cells were lower in children with SNI (n = 14). CD66b, was hyporesponsive and monocyte TLR4 was hyperresponsive to lipopolysaccharide in children with SNI compared to controls (n = 14). NLRP3 expression was higher at baseline and IL1β expression was not upregulated in response to lipopolysaccharide in children with SNI in contrast to controls.
We have found significant differences in immune regulation in children with SNI compared to controls which may provide a useful therapeutic target in the future.
Children with SNI have reduced monocyte and CD8+ T cells. Neutrophils and monocytes in children with SNI show altered markers of activation in response to lipopolysaccharide. Expression of NLRP3 at the RNA level was higher at baseline in children with SNI. This study adds to the existing literature that children with neurological impairment have altered inflammatory and immune cell responses. This may provide a useful therapeutic target to reduce infection-related morbidity and mortality, and tertiary neurological injury in the future.
感染会给患有严重神经功能障碍（SNI）的儿童带来严重的发病率和死亡率。已有报道称，神经功能障碍儿童的免疫细胞数量和功能发生改变。我们旨在比较 SNI 儿童与健康对照者的中性粒细胞、单核细胞和淋巴细胞比例及其对脂多糖刺激的反应，以确定其特征。
SNI 儿童和对照者的全血样本在存在或不存在脂多糖（10ng/ml）的情况下孵育。通过流式细胞术评估单核细胞和中性粒细胞功能（CD11b、TLR-4 和 CD66b 表达）和淋巴细胞。通过 PCR 评估参与炎症小体的基因（NLR 家族包含 pyrin 域（NLRP）-3、凋亡相关斑点样蛋白（ASC）和白细胞介素（IL）1β）的表达。
SNI 儿童的单核细胞和 CD8+T 细胞较低（n=14）。与对照组相比，SNI 儿童的 CD66b 反应较低，单核细胞 TLR4 对脂多糖的反应较高（n=14）。与对照组相比，SNI 儿童的 NLRP3 表达在基线时较高，而 IL1β 表达在脂多糖刺激下并未上调。
与对照组相比，SNI 儿童的免疫调节存在显著差异，这可能为未来提供有用的治疗靶点。
SNI 儿童的单核细胞和 CD8+T 细胞减少。SNI 儿童的中性粒细胞和单核细胞对脂多糖的反应显示出激活标志物的改变。SNI 儿童的 NLRP3 在基线时的 RNA 水平表达较高。本研究增加了现有的神经功能障碍儿童存在改变的炎症和免疫细胞反应的文献。这可能为减少未来与感染相关的发病率和死亡率以及三级神经损伤提供有用的治疗靶点。
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