加拿大麦克马斯特大学Zhou Xing团队近期取得重要工作进展，他们研究发现肠外卡介苗通过肠-肺轴诱导肺驻留记忆巨噬细胞和训练免疫。相关研究成果2022年12月1日在线发表于《自然—免疫学》杂志上。

据介绍，除了通过肠外注射疫苗或感染可以在骨髓（BM）和外周血中集中诱导训练免疫外，有证据表明，粘膜固有免疫记忆可通过黏膜暴露后的局部炎症途径产生。然而，黏膜固有记忆是否源于肠外接种/感染后远端产生的免疫信号的整合尚不清楚。

研究人员发现，皮下接种卡介苗（BCG）可诱导记忆性肺泡巨噬细胞（AM）和肺部的训练免疫。虽然肠外接种卡介苗可以训练脑脊髓炎祖细胞和循环单核细胞，但记忆性脑脊髓炎的诱导与循环单核细胞无关。相反，通过分枝杆菌传播的非肠道卡介苗接种会导致肠道微生物组、屏障功能和微生物代谢产物的时间依赖性变化，以及随后循环和肺部代谢产物的变化，从而导致AM诱导和肺部训练免疫。

总之，这些数据确定了肠道微生物群介导的远端粘膜组织先天免疫记忆发育途径，并对下一代针对呼吸道病原体疫苗的开发策略具有指导意义。

附：英文原文

Title: Parenteral BCG vaccine induces lung-resident memory macrophages and trained immunity via the gut–lung axis

Author: Jeyanathan, Mangalakumari, Vaseghi-Shanjani, Maryam, Afkhami, Sam, Grondin, Jensine A., Kang, Alisha, DAgostino, Michael R., Yao, Yushi, Jain, Shreya, Zganiacz, Anna, Kroezen, Zachary, Shanmuganathan, Meera, Singh, Ramandeep, Dvorkin-Gheva, Anna, Britz-McKibbin, Philip, Khan, Waliul I., Xing, Zhou

Issue&Volume: 2022-12-01

Abstract: Aside from centrally induced trained immunity in the bone marrow (BM) and peripheral blood by parenteral vaccination or infection, evidence indicates that mucosal-resident innate immune memory can develop via a local inflammatory pathway following mucosal exposure. However, whether mucosal-resident innate memory results from integrating distally generated immunological signals following parenteral vaccination/infection is unclear. Here we show that subcutaneous Bacillus Calmette–Guérin (BCG) vaccination can induce memory alveolar macrophages (AMs) and trained immunity in the lung. Although parenteral BCG vaccination trains BM progenitors and circulating monocytes, induction of memory AMs is independent of circulating monocytes. Rather, parenteral BCG vaccination, via mycobacterial dissemination, causes a time-dependent alteration in the intestinal microbiome, barrier function and microbial metabolites, and subsequent changes in circulating and lung metabolites, leading to the induction of memory macrophages and trained immunity in the lung. These data identify an intestinal microbiota-mediated pathway for innate immune memory development at distal mucosal tissues and have implications for the development of next-generation vaccine strategies against respiratory pathogens.

DOI: 10.1038/s41590-022-01354-4

Source: https://www.nature.com/articles/s41590-022-01354-4