Sphingosine-1-phosphate (S-1P) is a key sphingolipid involved in the pathobiology of various respiratory diseases. We have previously demonstrated the significance of S-1P in controlling non-pathogenic mycobacterial infection in macrophages, and here we demonstrate the therapeutic potential of S-1P against pathogenic Mycobacterium tuberculosis (H37Rv) in the mouse model of infection. Our study revealed that S-1P is involved in the expression of iNOS proteins in macrophages, their polarization toward M1 phenotype, and secretion of interferon (IFN)-γ during the course of infection. S-1P is also capable of enhancing infiltration of pulmonary CD11b+ macrophages and expression of S-1P receptor-3 (S-1PR3) in the lungs during the course of infection. We further revealed the influence of S-1P on major signaling components of inflammatory signaling pathways during M. tuberculosis infection, thus highlighting antimycobacterial potential of S-1P in animals. Our data suggest that enhancing S-1P levels by sphingolipid mimetic compounds/drugs can be used as an immunoadjuvant for boosting immunity against pathogenic mycobacteria.

中文翻译：

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1磷酸鞘氨醇（S-1P）促进幼稚巨噬细胞的分化并增强针对结核分枝杆菌的保护性免疫力。

鞘氨醇-1-磷酸酯（S-1P）是参与多种呼吸系统疾病病理生物学的关键鞘氨醇。我们以前已经证明了S-1P在控制巨噬细胞中非致病性分枝杆菌感染中的重要性，并且在这里我们证明了S-1P在小鼠感染模型中对病原性结核分枝杆菌（H37Rv）的治疗潜力。我们的研究表明，S-1P参与了iNOS蛋白在巨噬细胞中的表达，它们向M1表型的极化以及感染过程中干扰素（IFN）-γ的分泌。在感染过程中，S-1P还能够增强肺CD11b +巨噬细胞的浸润和肺中S-1P受体3（S-1PR3）的表达。我们进一步揭示了S-1P对结核分枝杆菌感染过程中炎症信号通路的主要信号传导成分的影响，从而突显了S-1P在动物体内的抗分枝杆菌潜力。我们的数据表明，通过类脂鞘脂类化合物/药物增强S-1P的水平可以用作免疫佐剂，以增强针对病原性分枝杆菌的免疫力。