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BCG 疫苗通过肠肺轴诱导肺驻留记忆巨噬细胞和训练性免疫。

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

机构信息

McMaster Immunology Research Centre, M. G. DeGroote Institute for Infectious Disease Research and Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Farncombe Family Digestive Health Research Institute and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

出版信息

Nat Immunol. 2022 Dec;23(12):1687-1702. doi: 10.1038/s41590-022-01354-4. Epub 2022 Dec 1.

DOI:10.1038/s41590-022-01354-4
PMID:36456739
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9747617/
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.

摘要

除了通过肠外接种或感染在骨髓 (BM) 和外周血中诱导中枢诱导的训练免疫外，有证据表明，黏膜固有免疫记忆可以通过黏膜暴露后的局部炎症途径发展。然而，黏膜固有免疫记忆是否来自肠外接种/感染后远处产生的免疫信号的整合尚不清楚。在这里，我们表明，皮下卡介苗 (BCG) 接种可以诱导肺部的记忆肺泡巨噬细胞 (AMs) 和训练免疫。尽管肠外 BCG 接种可训练 BM 祖细胞和循环单核细胞，但记忆 AM 的诱导不依赖于循环单核细胞。相反，通过分枝杆菌的传播，肠外 BCG 接种会导致肠道微生物组、屏障功能和微生物代谢物的时间依赖性改变，随后循环和肺部代谢物发生变化，导致肺部记忆巨噬细胞和训练免疫的诱导。这些数据确定了一种在远端黏膜组织中固有免疫记忆发展的肠道微生物群介导途径，并对开发针对呼吸道病原体的下一代疫苗策略具有重要意义。

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