Sphingosine-1-phosphate receptor 1 (S1PR1) plays a crucial role in infectious diseases. Targeting S1PR1 provides protection against pathogens, such as influenza viruses. This study is aimed at investigating S1PR1 in response to bacterial infection by assessing S1PR1 expression in S. aureus-infected mice. A rodent local muscle bacterial infection model was developed by injecting S. aureus to the lower hind limb of Balb/c mice. The changes of S1PR1 expression in response to bacterial infection and blocking treatment were assessed using ex vivo biodistribution and in vivo positron emission tomography (PET) after intravenous injection of an S1PR1-specific radiotracer [¹⁸F]TZ4877. The specificity of [¹⁸F]TZ4877 was assessed using S1PR1-specific antagonist, NIBR-0213, and S1PR1-specific DsiRNA pretreated the animals. Immunohistochemical studies were performed to confirm the increase of S1PR1 expression in response to infection. Ex vivo biodistribution data showed that the uptake of [¹⁸F]TZ4877 was increased 30.6%, 54.3%, 74.3%, and 115.3% in the liver, kidney, pancreas, and thymus of the infected mice, respectively, compared to that in normal control mice, indicating that S1PR1 is involved in the early immune response to bacterial infection. NIBR-0213 or S1PR1-specific DsiRNA pretreatment reduced the tissue uptake of [¹⁸F]TZ4877, suggesting that uptake of [¹⁸F]TZ4877 is specific. Our PET/CT study data also confirmed that infected mice have increased [¹⁸F]TZ4877 uptake in several organs comparing to that in normal control mice. Particularly, compared to control mice, a 39% increase of [¹⁸F]TZ4877 uptake was observed in the infected muscle of S. aureus mice, indicating that S1PR1 expression was directly involved in the inflammatory response to infection. Overall, our study suggested that S1PR1 plays an important role in the early immune response to bacterial infection. The uptake of [¹⁸F]TZ4877 is tightly correlated with the S1R1 expression in response to S. aureus infection. PET with S1PR1-specific radiotracer [¹⁸F]TZ4877 could provide a noninvasive tool for detecting the early S1PR1 immune response to infectious diseases.

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1-磷酸鞘氨醇受体 1 表达对金黄色葡萄球菌感染反应的 PET 研究

1-磷酸鞘氨醇受体 1 (S1PR1) 在传染病中起着至关重要的作用。靶向 S1PR1 可提供针对流感病毒等病原体的保护。本研究旨在通过评估金黄色葡萄球菌感染小鼠中的 S1PR1 表达来研究 S1PR1 对细菌感染的反应。通过将金黄色葡萄球菌注射到 Balb/c 小鼠的下肢，开发了啮齿动物局部肌肉细菌感染模型。^{在静脉注射 S1PR1 特异性放射性示踪剂 [ 18 F]TZ4877 后，使用离体生物分布和}体内正电子发射断层扫描 (PET)评估 S1PR1 表达响应细菌感染和阻断治疗的变化。^{[ 18}的特异性F]TZ4877 使用 S1PR1 特异性拮抗剂、NIBR-0213 和 S1PR1 特异性 DsiRNA 预处理动物进行评估。进行免疫组织化学研究以确认 S1PR1 表达增加以响应感染。离体生物分布数据显示，与正常小鼠相比，感染小鼠的肝脏、肾脏、胰腺和胸腺中 [ 18 F]TZ4877 的摄取分别增加了 30.6%、54.3%、74.3% 和^115.3 %对照小鼠，表明 S1PR1 参与了对细菌感染的早期免疫反应。^{NIBR-0213 或 S1PR1 特异性 DsiRNA 预处理减少了 [ 18} F]TZ4877的组织摄取，表明 [ ¹⁸F]TZ4877 是特定的。我们的 PET/CT 研究数据还证实，与正常对照小鼠相比，受感染的小鼠在几个器官中增加了 [ ^{18 F]TZ4877 摄取。}特别地，与对照小鼠相比，在金黄色葡萄球菌小鼠的受感染肌肉中观察到[ ¹⁸ F]TZ4877 摄取增加 39% ，表明 S1PR1 表达直接参与对感染的炎症反应。总的来说，我们的研究表明 S1PR1 在细菌感染的早期免疫反应中起着重要作用。^{[ 18} F]TZ4877的摄取与响应金黄色葡萄球菌感染的 S1R1 表达密切相关。带有 S1PR1 特异性放射性示踪剂的 PET [ ¹⁸F]TZ4877 可以提供一种无创工具，用于检测早期 S1PR1 对传染病的免疫反应。