美国斯坦福大学Bali Pulendran团队发现，卡介苗接种通过反馈适应性免疫反应来刺激综合器官免疫，从而形成长期的先天性抗病毒能力。该项研究成果于2023年11月30日在线发表在《自然—免疫学》杂志上。

研究人员表明，静脉注射卡介苗（Bacille Calmette-Guérin，BCG）的小鼠在受到严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2 B.1.351）或PR8流感病毒的感染时，体重减轻和/或病毒清除率提高。保护作用在接种后14至21天首次显现，并持续3个月。值得注意的是，BCG在肺部诱导了双相先天性反应和强大的抗原特异性1型辅助T细胞（T_H1细胞）反应。MyD88信号传导对先天性和T_H1细胞反应以及对SARS-CoV-2的保护至关重要。在感染前消耗CD4⁺ T细胞或干扰素（IFN）-γ活性可消除先天性激活和保护作用。

单细胞和空间转录组学显示，在肺髓细胞和上皮细胞中，IFN刺激基因的表达依赖于CD4。值得注意的是，BCG还能诱导小鼠适应SARS-CoV-2 BA.5、SARS-CoV和SHC014冠状病毒感染后的体重减轻。因此，BCG可诱导综合器官免疫，CD4⁺ T细胞可反馈到组织髓系细胞和上皮细胞，从而形成持久而广泛的先天性抗病毒能力。

据了解，接种BCG可提供针对异源病原体的非特异性保护。然而，其潜在机制仍是一个谜。

附：英文原文

Title: BCG vaccination stimulates integrated organ immunity by feedback of the adaptive immune response to imprint prolonged innate antiviral resistance

Author: Lee, Audrey, Floyd, Katharine, Wu, Shengyang, Fang, Zhuoqing, Tan, Tze Kai, Froggatt, Heather M., Powers, John M., Leist, Sarah R., Gully, Kendra L., Hubbard, Miranda L., Li, Chunfeng, Hui, Harold, Scoville, David, Ruggiero, Alistaire D., Liang, Yan, Pavenko, Anna, Lujan, Victor, Baric, Ralph S., Nolan, Garry P., Arunachalam, Prabhu S., Suthar, Mehul S., Pulendran, Bali

Issue&Volume: 2023-11-30

Abstract: Bacille Calmette–Guérin (BCG) vaccination can confer nonspecific protection against heterologous pathogens. However, the underlying mechanisms remain mysterious. We show that mice vaccinated intravenously with BCG exhibited reduced weight loss and/or improved viral clearance when challenged with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 B.1.351) or PR8 influenza. Protection was first evident between 14 and 21d post-vaccination and lasted ～3months. Notably, BCG induced a biphasic innate response and robust antigen-specific type 1 helper T cell (TH1 cell) responses in the lungs. MyD88 signaling was essential for innate and TH1 cell responses, and protection against SARS-CoV-2. Depletion of CD4+ T cells or interferon (IFN)-γ activity before infection obliterated innate activation and protection. Single-cell and spatial transcriptomics revealed CD4-dependent expression of IFN-stimulated genes in lung myeloid and epithelial cells. Notably, BCG also induced protection against weight loss after mouse-adapted SARS-CoV-2 BA.5, SARS-CoV and SHC014 coronavirus infections. Thus, BCG elicits integrated organ immunity, where CD4+ T cells feed back on tissue myeloid and epithelial cells to imprint prolonged and broad innate antiviral resistance.

DOI: 10.1038/s41590-023-01700-0

Source: https://www.nature.com/articles/s41590-023-01700-0