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免疫检查点分子作为黄金葡萄球菌的生物标志物骨感染和临床结果

Motoo Saito¹, Katya A McDonald^1,2, Alex K Grier³

¹The Center for Musculoskeletal Research, Department of Orthopedics, University of Rochester Medical Center, Rochester, NY, USA.

bioRxiv : the preprint server for biology

|January 13, 2025

概括

黄金葡萄球菌假肢关节感染 (PJI) 显示T细胞耗尽和免疫检查点蛋白上调. 这些发现表明PJI结果和治疗目标的潜在生物标志物.

科学领域:

免疫学免疫学免疫学
微生物学微生物学
翻译医学是一种翻译医学.

背景情况:

由黄金葡萄球菌引起的假肢关节感染 (PJIs) 难以治疗,缺乏用于治疗决策的诊断工具.
目前对S. aureus PJIs宿主免疫反应的理解有限,这阻碍了有效的治疗策略.

研究的目的:

在S. aureus PJI的人性化小鼠模型中研究T细胞的异质性和功能.
为了确定S. aureus PJI疾病严重程度和结果的潜在诊断生物标志物.
探索免疫检查点封锁作为S. aureus PJI的潜在治疗策略.

主要方法:

利用一个人性化的NSG-SGM3 BLT小鼠模型与多omics分析来研究T细胞反应.
在小鼠模型和人类PJI患者样本 (血清和骨髓) 中分析了免疫检查点蛋白 (LAG3,TIM-3) 和细胞因子的基因表达和蛋白质水平.
开发了一种结合免疫检查点蛋白和细胞因子水平的多参数名录,以预测疾病的结果.

主要成果:

在小鼠模型中,人类T细胞表现出显著的异质性,包括激活的,祖先耗尽的和终极耗尽的Th1/Th17种群.
免疫检查点蛋白 (LAG3,TIM-3) 在小鼠模型和人类S. aureus PJI患者中都被上调.
高水平的TIM-3,结合低水平的促炎细胞因子 (IFN-γ,IL-2,TNF-α,IL-17),对不良PJI结果的高度预测 (AUC=0.89).

结论:

具有免疫检查点表达和疲劳特征的T细胞损伤作为S. aureus PJI的潜在功能生物标志物.
免疫检查点封锁可能是一个有希望的治疗途径,以改善S. aureus PJI患者的结果.
对T细胞动态和免疫检查点的进一步研究对于开发S. aureus PJIs的新型诊断和治疗策略至关重要.

关键词:

黄金葡萄球菌黄金葡萄球菌 T细胞耗尽的情况主体-病原体相互作用免疫检查点蛋白质的免疫检查点蛋白质骨质炎是一种骨质炎.我们的 scRNAseqq.

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