Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Institute for Infection and Immunity, St. George's University of London, London, United Kingdom.
Front Immunol. 2022 Aug 12;13:993495. doi: 10.3389/fimmu.2022.993495. eCollection 2022.
The cerebrospinal fluid (CSF) immune responses in HIV-uninfected cryptococcal meningitis (CM) have not been well studied. In this study, we aimed to explore the phenotype of CSF immune response during the course of disease and to examine relationships between phenotypes and disease severity. We profiled the CSF immune response in 128 HIV-uninfected CM and 30 pulmonary cryptococcosis patients using a 27-plex Luminex cytokine kit. Principal component analyses (PCA) and logistic regression model were performed. Concentrations of 23 out of 27 cytokines and chemokines in baseline CSF were significantly elevated in CM patients compared with pulmonary cryptococcosis cases. In CM patients with infection, IL-1ra, IL-9, and VEGF were significantly elevated in immunocompetent cases. Cytokine levels usually reached peaks within the first 2 weeks of antifungal treatment and gradually decreased over time. PCA demonstrated a co-correlated CSF cytokine and chemokine response consisting of Th1, Th2, and Th17 type cytokines. Prognostic analysis showed that higher scores for the PCs loading pro-inflammatory cytokines, IFN-γ, TNF-α, and IL-12; and anti-inflammatory cytokine, IL-4; and chemokines, Eotaxin, FGF-basis, and PDGF-bb; as well as lower scores for the PCs loading RANTES were associated with disease severity, as defined by a Glasgow Coma Scale of <15 or death. In conclusion, combined inflammatory responses in CSF involving both pro- and anti-inflammatory cytokines and chemokines are upregulated in HIV-uninfected CM, and associated with disease severity.
未感染 HIV 的隐球菌性脑膜炎（CM）患者的脑脊液（CSF）免疫反应尚未得到充分研究。在本研究中，我们旨在探索疾病过程中 CSF 免疫反应的表型，并研究表型与疾病严重程度之间的关系。我们使用 27 plex Luminex 细胞因子试剂盒对 128 例未感染 HIV 的 CM 患者和 30 例肺部隐球菌病患者的 CSF 免疫反应进行了分析。进行了主成分分析（PCA）和逻辑回归模型分析。与肺部隐球菌病病例相比，CM 患者基线 CSF 中的 27 种细胞因子和趋化因子中的 23 种浓度明显升高。在有 感染的 CM 患者中，免疫功能正常的患者中 IL-1ra、IL-9 和 VEGF 明显升高。细胞因子水平通常在抗真菌治疗的前 2 周内达到峰值，随后逐渐下降。PCA 显示出与 Th1、Th2 和 Th17 型细胞因子相关的 CSF 细胞因子和趋化因子的共同相关反应。预后分析显示，加载促炎细胞因子 IFN-γ、TNF-α 和 IL-12 的 PC 评分较高；抗炎细胞因子 IL-4；和趋化因子 Eotaxin、FGF-basis 和 PDGF-bb；以及加载 RANTES 的 PC 评分较低，与疾病严重程度相关，定义为格拉斯哥昏迷量表<15 或死亡。总之，HIV 未感染的 CM 患者的 CSF 中涉及促炎和抗炎细胞因子和趋化因子的联合炎症反应上调，并与疾病严重程度相关。
