Toll-Like Receptor (TLR) 9 stimulation is required for induction of potent immune responses against pathogen invasion. The use of unmethylated CpG as adjuvants in vaccines provides an excellent means of stimulating adaptive immunity. Our data demonstrate that CpG-C provided prolonged immune responses in the mouse model of tuberculosis when formulated with liposomes and the Mycobacterium tuberculosis antigen ESAT-6. A reduction in the mycobacterial burden was best achieved when administered as an intranasal vaccine and was dependent on type I interferon (IFN). There was a significant difference between CpG-C inoculated wild type and IFN-αR1-/- mice, indicating that type I IFN plays a role in the immune response following CpG-C inoculation. Further analysis showed that early NK cell presence was not an absolute requirement, although elevated IFN-γ levels were detected in the lungs of mice within 48 h. The reduction in mycobacterial burden was MyD88-independent as CpG-C inoculated MyD88-/- mice showed comparable mycobacterial burdens to wild type mice with no detriment due to the lack of MyD88. Together our data show that pulmonary stimulation of TLR9 bearing antigen presenting cells resulted in the induction of protective immunity against M. tuberculosis infection that was dependent on type I IFN signaling.

中文翻译：

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在小鼠模型中，通过 CpG 介导的肺黏膜免疫为抵抗肺结核分枝杆菌感染提供了足够的保护。I型干扰素的作用

Toll 样受体 (TLR) 9 刺激是诱导针对病原体入侵的有效免疫反应所必需的。在疫苗中使用未甲基化的 CpG 作为佐剂提供了一种极好的刺激适应性免疫的方法。我们的数据表明，当与脂质体和结核分枝杆菌抗原 ESAT-6 一起配制时，CpG-C 在结核病小鼠模型中提供延长的免疫反应。当作为鼻内疫苗给药并且依赖于 I 型干扰素 (IFN) 时，可以最好地减少分枝杆菌负担。CpG-C 接种的野生型和 IFN-αR1-/- 小鼠之间存在显着差异，表明 I 型 IFN 在 CpG-C 接种后的免疫反应中起作用。进一步的分析表明，早期 NK 细胞的存在并不是绝对的要求，尽管在 48 小时内在小鼠肺中检测到 IFN-γ 水平升高。分枝杆菌负荷的减少与 MyD88 无关，因为接种 CpG-C 的 MyD88-/- 小鼠表现出与野生型小鼠相当的分枝杆菌负荷，而没有由于缺乏 MyD88 而造成损害。我们的数据一起显示，对带有 TLR9 的抗原呈递细胞的肺刺激导致诱导针对结核分枝杆菌感染的保护性免疫，这种免疫依赖于 I 型 IFN 信号传导。