BCG trains lung macrophages
Bacillus Calmette-Guerin (BCG) is an attenuated mycobacterial vaccine historically used to protect against Mycobacterium tuberculosis (Mtb), and intradermal BCG vaccination has modest efficacy. Mata et al. now define immune mechanisms associated with protection induced by pulmonary BCG administration. They observed that mice vaccinated with BCG via pulmonary delivery were able to limit early dissemination of Mtb upon challenge. Long-term protection was also observed and was linked to BCG-mediated activation of alveolar macrophages (AMs) that were rapidly reactivated upon challenge, suggesting a role for trained immunity. These results highlight the potential of intrapulmonary BCG challenge and the role of AMs in protection against Mtb.
卡介苗 (BCG) 是一种减毒分枝杆菌疫苗，历史上用于预防结核分枝杆菌( Mtb )，皮内注射 BCG 疫苗具有中等功效。现在定义与肺 BCG 给药诱导的保护相关的免疫机制。他们观察到，通过肺部递送接种 BCG 的小鼠能够限制Mtb在受到攻击时的早期传播。还观察到了长期保护，并且与 BCG 介导的肺泡巨噬细胞 (AM) 激活有关，这些巨噬细胞在受到攻击时会迅速重新激活，这表明训练免疫的作用。这些结果突出了肺内 BCG 挑战的潜力和 AMs 在预防结核杆菌。
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.
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极大的兴趣，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，对经过绿色荧光蛋白标记的有毒 ( Mtb ) 和减毒 (BCG) 分枝杆菌菌株进行肺部递送的小鼠进行了研究，以更好地表征受感染的肺细胞亚群。之间检测到在传播模式深刻分歧的Mtb和BCG，具有的强烈倾向的Mtb从肺泡巨噬细胞 (AMs) 传播到其他髓系亚群，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后能非常有效地包含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性肺炎链球菌的攻击，这表明 BCG 诱导的先天激活可以赋予与Mtb不同的呼吸道病原体的异源保护. 即使在疫苗清除后，BCG 也能驱动 AMs 的长期激活，并且这些 AMs 在随后的挑战中做出有效反应。这些结果表明在肺 BCG 疫苗接种诱导的 AM 中产生了训练有素的先天记忆样反应。