BACKGROUND Individuals with impaired immunity are more susceptible to infections than immunocompetent subjects. No vaccines are currently available to induce protection against E. coli meningoencephalitis. This study evaluated the potential of poly(I:C) pre-treatment to induce trained immunity. Poly(I:C) was administered as a non-specific stimulus of innate immune responses to protect immunocompetent and neutropenic wild-type mice from a subsequent challenge by the intracranial injection of E. coli K1. METHODS Three days prior to infection, mice received an intraperitoneal injection of poly(I:C) or vehicle. Kaplan-Meier survival curves were analyzed. In short-term experiments, bacterial titers and the inflammatory response were characterized in the blood, cerebellum, and spleen homogenates. NK cell subpopulations in the brain and spleen were analyzed by flow cytometry. Numbers of microglia and activation scores were evaluated by histopathology. RESULTS Pre-treatment with 200 μg poly(I:C) increased survival time, reduced mortality, and enhanced bacterial clearance in the blood, cerebellum, and spleen at early infection in neutropenic mice. Poly(I:C)-mediated protection correlated with an augmented number of NK cells (CD45+NK1.1+CD3-) and Iba-1+ microglial cells and a higher production of IFN-γ in the brain. In the spleen, levels of CCL5/RANTES and IFN-γ were increased and sustained in surviving poly(I:C)-treated animals for 14 days after infection. In immunocompetent animals, survival time was not significantly prolonged in poly(I:C)-treated animals although poly(I:C) priming reduced brain bacterial concentrations compared with vehicle-injected animals at early infection. CONCLUSIONS Pre-treatment with the viral TLR3 agonist poly(I:C) modulated innate immune responses and strengthened the resistance of neutropenic mice against E. coli K1 meningoencephalitis.

中文翻译：

---

用病毒Toll样受体3激动剂poly（I：C）进行预处理可调节先天免疫力，并保护脑内感染大肠杆菌的嗜中性白血球减少症小鼠。

背景技术与免疫能力强的受试者相比，免疫力受损的个体更容易受到感染。当前没有疫苗可诱导针对大肠杆菌脑膜脑炎的保护。这项研究评估了聚（I：C）预处理诱导训练性免疫的潜力。Poly（I：C）作为先天性免疫应答的非特异性刺激物进行给药，以通过颅内注射E. coli K1保护免疫能力强和中性粒细胞减少的野生型小鼠免受随后的攻击。方法感染前三天，小鼠接受腹腔注射聚（I：C）或媒介物。分析了Kaplan-Meier生存曲线。在短期实验中，在血液，小脑和脾匀浆中鉴定了细菌滴度和炎症反应。通过流式细胞仪分析脑和脾中的NK细胞亚群。通过组织病理学评估小胶质细胞的数目和活化分数。结果在中性粒细胞减少的小鼠中，用200μg聚（I：C）进行预处理可延长生存时间，降低死亡率，并增强血液，小脑和脾脏中细菌的清除率。聚（I：C）介导的保护与NK细胞（CD45 + NK1.1 + CD3-）和Iba-1 +小胶质细胞数量的增加以及脑中IFN-γ的更高产生有关。在存活的经聚（I：C）处理的动物中，脾脏中的CCL5 / RANTES和IFN-γ的水平升高并持续了14天。在具有免疫能力的动物中，尽管采用聚（I：C）处理的动物，其存活时间并未明显延长 C）与在早期感染时用媒介物注射的动物相比，引发降低的脑细菌浓度。结论病毒TLR3激动剂聚（I：C）预处理可调节先天免疫应答并增强中性粒细胞减少性小鼠对大肠杆菌K1脑膜脑炎的抵抗力。