After a century of using the Bacillus Calmette–Guérin (BCG) vaccine, our understanding of its ability to provide protection against homologous (Mycobacterium tuberculosis) or heterologous (for example, influenza virus) infections remains limited. Here we show that systemic (intravenous) BCG vaccination provides significant protection against subsequent influenza A virus infection in mice. We further demonstrate that the BCG-mediated cross-protection against influenza A virus is largely due to the enrichment of conventional CD4⁺ effector CX3CR1^hi memory αβ T cells in the circulation and lung parenchyma. Importantly, pulmonary CX3CR1^hi T cells limit early viral infection in an antigen-independent manner via potent interferon-γ production, which subsequently enhances long-term antimicrobial activity of alveolar macrophages. These results offer insight into the unknown mechanism by which BCG has persistently displayed broad protection against non-tuberculosis infections via cross-talk between adaptive and innate memory responses.

使用卡介苗 (BCG) 疫苗一个世纪后，我们对其针对同源（结核分枝杆菌）或异源（例如流感病毒）感染提供保护的能力的了解仍然有限。在这里，我们表明，全身（静脉注射）卡介苗疫苗接种可以显着保护小鼠免受随后的甲型流感病毒感染。我们进一步证明，BCG 介导的针对甲型流感病毒的交叉保护很大程度上是由于循环和肺实质中传统 CD4 ⁺效应器 CX3CR1 ^hi记忆 αβ T 细胞的富集。重要的是，肺部 CX3CR1 ^hi T 细胞通过有效的干扰素 γ 产生，以不依赖于抗原的方式限制早期病毒感染，从而增强肺泡巨噬细胞的长期抗菌活性。这些结果提供了对未知机制的深入了解，卡介苗通过适应性记忆反应和先天记忆反应之间的串扰，持续显示出针对非结核病感染的广泛保护作用。