Bacillus Calmette-Guerin (BCG) is an attenuated bacterial vaccine used to protect against Mycobacterium tuberculosis (Mtb) in regions where infections are highly prevalent. BCG is currently delivered by the intradermal route, but alternative routes of administration are of great interest, including intrapulmonary delivery to more closely mimic respiratory Mtb infection. In this study, mice subjected to pulmonary delivery of green fluorescent protein–tagged strains of virulent (Mtb) and attenuated (BCG) mycobacteria were studied to better characterize infected lung cell subsets. Profound differences in dissemination patterns were detected between Mtb and BCG, with a strong tendency of Mtb to disseminate from alveolar macrophages (AMs) to other myeloid subsets, mainly neutrophils and recruited macrophages. BCG mostly remained in AMs, which promoted their activation. These preactivated macrophages were highly efficient in containing Mtb bacilli upon challenge and disrupting early bacterial dissemination, which suggests a potential mechanism of protection associated with pulmonary BCG vaccination. Respiratory BCG also protected mice against a lethal Streptococcus pneumoniae challenge, suggesting that BCG-induced innate activation could confer heterologous protection against respiratory pathogens different from Mtb. BCG drove long-term activation of AMs, even after vaccine clearance, and these AMs reacted efficiently upon subsequent challenge. These results suggest the generation of a trained innate memory-like response in AMs induced by pulmonary BCG vaccination.

中文翻译：

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肺卡介苗诱导肺内巨噬细胞活化并提供长期抗结核病保护

卡介苗 (BCG) 是一种减毒细菌疫苗，用于在感染高度流行的地区预防结核分枝杆菌( Mtb )。BCG 目前通过皮内途径递送，但其他给药途径引起了人们的极大兴趣，包括肺内递送以更接近地模拟呼吸道Mtb感染。在这项研究中，研究了经肺部递送绿色荧光蛋白标记的毒性 ( Mtb ) 和减毒 (BCG) 分枝杆菌菌株的小鼠，以更好地表征受感染的肺细胞亚群。在Mtb和 BCG之间检测到传播模式存在显着差异，Mtb的趋势很强从肺泡巨噬细胞 (AMs) 传播到其他骨髓亚群，主要是中性粒细胞和募集的巨噬细胞。BCG 主要保留在 AMs 中，这促进了它们的激活。这些预活化的巨噬细胞在攻击时能高效地抑制Mtb杆菌并破坏早期细菌传播，这表明与肺 BCG 疫苗接种相关的潜在保护机制。呼吸道 BCG 还保护小鼠免受致命的肺炎链球菌攻击，这表明 BCG 诱导的先天激活可以赋予对不同于Mtb的呼吸道病原体的异源保护. BCG 驱动 AMs 的长期激活，即使在疫苗清除后，这些 AMs 在随后的挑战中也能有效地作出反应。这些结果表明在肺卡介苗接种诱导的 AMs 中产生了训练有素的先天记忆样反应。