The CSF transcriptome in adults with pneumococcal meningitis reveals compartmentalised host inflammatory responses associated with mortality

IF 2.8 4区医学 Q3 IMMUNOLOGY

Immunology letters Pub Date : 2025-07-07 DOI:10.1016/j.imlet.2025.107059

José Afonso Guerra-Assunção , Probir Chakravarty , Gabriele Pollara , Cristina Venturini , Veronica S Mlozowa , Brigitte Denis , Mulinda Nyirenda , David G Lalloo , Mahdad Noursadeghi , Jeremy S Brown , Robert S Heyderman , Emma C Wall

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引用次数: 0

Abstract

Pneumococcal meningitis (PM) has persistently poor clinical outcomes, especially in sub-Saharan Africa. To better characterise the inflammatory response and identify factors associated with mortality we compared paired peripheral blood and cerebrospinal fluid (CSF) transcriptomes before the initiation of antibiotics in Malawian adults with proven PM.

Blood transcriptional profiles were obtained in 28 patients with PM, with simultaneous paired with CSF profiles available for 13 patients. 15/28 (52 %) patients died. Comparison of the transcriptome between CSF and blood compartments showed upregulation of 2293 differentially expressed genes in CSF and 909 in blood; enriched pathways in CSF included inflammasome activity and neutrophil migration/activation, contrasting with enrichment for pathways including platelet and endothelial activation, cell cycle, cytokine release and oxidative stress in the blood transcriptome. Comparison of CSF profiles between survivors and non-survivors revealed 1829 differentially expressed genes. Non-survivor CSF was enriched for multiple innate inflammatory pathways, including IL-17A and Type 1 interferons and proteolysis. In contrast, minimal transcriptomic differences between outcome groups were detected in blood.

Inflammation in PM is characterised by compartmentalised responses in blood and CSF. Poorer outcomes are associated with an dysregulated innate immune host response to S. pneumoniae in the CSF compartment.

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成人肺炎球菌脑膜炎的脑脊液转录组揭示了与死亡率相关的区隔宿主炎症反应。

肺炎球菌脑膜炎（PM）的临床结果一直很差，特别是在撒哈拉以南非洲。为了更好地表征炎症反应并确定与死亡率相关的因素，我们比较了马拉维成年确诊PM患者在开始使用抗生素之前的成对外周血和脑脊液（CSF）转录组。在28例PM患者中获得了血液转录谱，同时配对了13例患者的CSF谱。15/28（52%）患者死亡。脑脊液与血室的转录组比较显示，脑脊液中有2293个差异表达基因上调，血室中有909个差异表达基因上调；脑脊液中富集的途径包括炎性体活性和中性粒细胞迁移/活化，而血液转录组中富集的途径包括血小板和内皮活化、细胞周期、细胞因子释放和氧化应激。幸存者和非幸存者的脑脊液谱比较发现了1829个差异表达基因。非幸存者CSF富含多种先天性炎症途径，包括IL-17A和1型干扰素和蛋白水解。相比之下，在血液中检测到结果组之间的转录组差异很小。PM炎症的特征是血液和脑脊液的区隔反应。较差的结果与先天性免疫宿主对脑脊液室肺炎链球菌反应失调有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunology letters 医学-免疫学

CiteScore

7.60

自引率

0.00%

发文量

审稿时长

44 days

期刊介绍： Immunology Letters provides a vehicle for the speedy publication of experimental papers, (mini)Reviews and Letters to the Editor addressing all aspects of molecular and cellular immunology. The essential criteria for publication will be clarity, experimental soundness and novelty. Results contradictory to current accepted thinking or ideas divergent from actual dogmas will be considered for publication provided that they are based on solid experimental findings. Preference will be given to papers of immediate importance to other investigators, either by their experimental data, new ideas or new methodology. Scientific correspondence to the Editor-in-Chief related to the published papers may also be accepted provided that they are short and scientifically relevant to the papers mentioned, in order to provide a continuing forum for discussion.