加拿大麦吉尔大学Maziar Divangahi小组发现，卡介苗免疫诱导CX3CR1^hi效应记忆T细胞通过IFN-γ介导的训练免疫来提供交叉保护。2024年1月15日，国际知名学术期刊《自然—免疫学》在线发表了这一成果。

研究人员表示，卡介苗（Bacillus Calmette-Guérin，简称BCG）已经使用了一个世纪，但人们对它在同源（结核分枝杆菌）或异源（如流感病毒）感染中提供保护的能力的了解仍然有限。

研究人员证明全身（静脉）接种BCG可显著保护小鼠免受随后的甲型流感病毒感染。研究人员进一步证明，BCG介导的对甲型流感病毒的交叉保护主要是由于循环和肺实质中常规CD4⁺效应细胞CX3CR1^hi记忆αβ T细胞的富集。重要的是，肺CX3CR1^hiT细胞通过产生强效干扰素-γ，以抗原无关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。这些结果使人们深入了解了BCG通过适应性和先天性记忆反应之间的交叉对话，对非结核感染持续提供广泛保护的未知机制。

附：英文原文

Title: BCG immunization induces CX3CR1hi effector memory T cells to provide cross-protection via IFN-γ-mediated trained immunity

Author: Tran, Kim A., Pernet, Erwan, Sadeghi, Mina, Downey, Jeffrey, Chronopoulos, Julia, Lapshina, Elizabeth, Tsai, Oscar, Kaufmann, Eva, Ding, Jun, Divangahi, Maziar

Issue&Volume: 2024-01-15

Abstract: 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 CX3CR1hi memory αβ T cells in the circulation and lung parenchyma. Importantly, pulmonary CX3CR1hi 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.

DOI: 10.1038/s41590-023-01739-z

Source: https://www.nature.com/articles/s41590-023-01739-z