Zhang Yujie, Duan Jing, Lin Sufang, Wen Jialun, Liao Jianxiang
Department of Neurology, Shenzhen Children's Hospital, No. 7019 Yitian Road, Futian District, Shenzhen, China.
Sci Rep. 2025 May 22;15(1):17795. doi: 10.1038/s41598-025-02258-7.
Streptococcus pneumoniae, a Gram-positive, human-specific commensal infectious pathogen, poses a significant global health threat, especially in children under five, often resulting in fatalities. The intricacies of the immune response in pneumococcal meningitis (PM) remain elusive, necessitating a meticulous examination of immune cell subsets at the single-cell resolution. In this study, we performed single-cell RNA sequencing of peripheral blood mononuclear cells from PM patients and healthy individuals. We found significant relative changes in the compositions of immune cell subset, with significant relative increases in platelets, neutrophils, and their precursors, alongside relative decreases in natural killer (NK) cells, T cell subtypes, and plasmacytoid dendritic cells in PM patients. Functional enrichment analyses revealed an up-regulation of neutrophils-related immune genes across multiple immune cell types, including platelets, myeloid cells and B cells, suggesting excessive neutrophil activation. However, a down-regulation of genes involved in antigen processing and presentation in myeloid cells and B cells in the PM group indicated a relative dampening of the adaptive immune response in the PM patients. This was further corroborated by the reduced proportions of plasmacytoid dendritic cells and T cells. Furthermore, genes involved in cytotoxity were down-regulated in both NK cells and T cells, alongside impaired T cell activation. Notably, distinct B cell subtypes, including unique naïve B cell clusters, demonstrated differentially expressed genes associated with both innate and adaptive immune responses. In conclusion, our study provides a comprehensive single-cell transcriptomic landscape of immune responses in PM. The identified cellular and molecular signatures offer potential targets for therapeutic intervention and provide a foundation for further investigation into the immunopathogenesis of pneumococcal meningitis.
肺炎链球菌是一种革兰氏阳性、人类特异性共生感染病原体，对全球健康构成重大威胁，尤其是对五岁以下儿童，常常导致死亡。肺炎球菌性脑膜炎（PM）中免疫反应的复杂性仍然难以捉摸，因此有必要在单细胞分辨率下对免疫细胞亚群进行细致检查。在本研究中，我们对PM患者和健康个体的外周血单核细胞进行了单细胞RNA测序。我们发现免疫细胞亚群的组成有显著的相对变化，PM患者的血小板、中性粒细胞及其前体显著相对增加，而自然杀伤（NK）细胞、T细胞亚型和浆细胞样树突状细胞相对减少。功能富集分析显示，包括血小板、髓样细胞和B细胞在内的多种免疫细胞类型中，与中性粒细胞相关的免疫基因上调，表明中性粒细胞过度活化。然而，PM组中髓样细胞和B细胞中参与抗原加工和呈递的基因下调，表明PM患者的适应性免疫反应相对受到抑制。浆细胞样树突状细胞和T细胞比例降低进一步证实了这一点。此外，NK细胞和T细胞中参与细胞毒性的基因下调，同时T细胞活化受损。值得注意的是，不同的B细胞亚型，包括独特的初始B细胞簇，表现出与先天和适应性免疫反应相关的差异表达基因。总之，我们的研究提供了PM免疫反应全面的单细胞转录组图谱。所确定的细胞和分子特征为治疗干预提供了潜在靶点，并为进一步研究肺炎球菌性脑膜炎的免疫发病机制奠定了基础。
