Peters Joshua M, Irvine Edward B, Makatsa Mohau S, Rosenberg Jacob M, Wadsworth Marc H, Hughes Travis K, Sutton Matthew S, Nyquist Sarah K, Bromley Joshua D, Mondal Rajib, Roederer Mario, Seder Robert A, Darrah Patricia A, Alter Galit, Seshadri Chetan, Flynn JoAnne L, Shalek Alex K, Fortune Sarah M, Bryson Bryan D
Department of Biological Engineering, MIT, Cambridge, MA, USA.
Ragon Institute of MGH, Harvard, and MIT, Cambridge, MA, USA.
Sci Adv. 2025 Jan 3;11(1):eadq8229. doi: 10.1126/sciadv.adq8229. Epub 2025 Jan 1.
Intradermal Bacillus Calmette-Guérin (BCG) is the most widely administered vaccine, but it does not sufficiently protect adults against pulmonary tuberculosis. Recent studies in nonhuman primates show that intravenous BCG administration offers superior protection against (). We used single-cell analysis of bronchoalveolar lavage cells from rhesus macaques vaccinated via different routes and doses of BCG to identify alterations in the immune ecosystem in the airway following vaccination. Our findings reveal that high-dose intravenous BCG induces an influx of polyfunctional T cells and macrophages in the airways, with alveolar macrophages from high-dose intravenous BCG displaying a basal activation state in the absence of purified protein derivative stimulation, defined in part by interferon signaling. Enhanced intercellular immune signaling and stronger T helper 1-T helper 17 transcriptional responses were observed following purified protein derivative stimulation. These results suggest that high-dose intravenous BCG vaccination creates a specialized immune environment that primes airway cells for effective clearance.
皮内注射卡介苗（BCG）是使用最广泛的疫苗，但它对成人肺结核的保护作用并不充分。最近在非人类灵长类动物中的研究表明，静脉注射卡介苗能提供更好的保护作用以抵御（）。我们对通过不同途径和剂量接种卡介苗的恒河猴的支气管肺泡灌洗细胞进行单细胞分析，以确定接种疫苗后气道免疫生态系统的变化。我们的研究结果显示，高剂量静脉注射卡介苗会诱导多功能T细胞和巨噬细胞流入气道，高剂量静脉注射卡介苗组的肺泡巨噬细胞在无纯化蛋白衍生物刺激的情况下呈现基础激活状态，部分由干扰素信号传导所定义。在纯化蛋白衍生物刺激后，观察到细胞间免疫信号增强以及更强的辅助性T细胞1 - 辅助性T细胞17转录反应。这些结果表明，高剂量静脉注射卡介苗接种可创造一个特殊的免疫环境，使气道细胞做好有效清除的准备。
