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人体卡介苗接种通过造血祖细胞区室诱导训练有素的免疫。

BCG Vaccination in Humans Elicits Trained Immunity via the Hematopoietic Progenitor Compartment.

机构信息

Quantitative Systems Biology, Life & Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany.

Department of Internal Medicine, Radboud Institute of Molecular Life Sciences (RIMLS) and Radboud Center for Infectious Diseases (RCI), Radboud University Nijmegen Medical Centre, 6526 GA Nijmegen, the Netherlands; Research Center for Vitamins and Vaccines, Bandim Health Project, Statens Serum Institut, Copenhagen, Denmark; Odense Patient Data Explorative Network, University of Southern Denmark/Odense University Hospital, Odense, Denmark.

出版信息

Cell Host Microbe. 2020 Aug 12;28(2):322-334.e5. doi: 10.1016/j.chom.2020.05.014. Epub 2020 Jun 15.

DOI:10.1016/j.chom.2020.05.014
PMID:32544459
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7295478/
Abstract

Induction of trained immunity by Bacille-Calmette-Guérin (BCG) vaccination mediates beneficial heterologous effects, but the mechanisms underlying its persistence and magnitude remain elusive. In this study, we show that BCG vaccination in healthy human volunteers induces a persistent transcriptional program connected to myeloid cell development and function within the hematopoietic stem and progenitor cell (HSPC) compartment in the bone marrow. We identify hepatic nuclear factor (HNF) family members 1a and b as crucial regulators of this transcriptional shift. These findings are corroborated by higher granulocyte numbers in BCG-vaccinated infants, HNF1 SNP variants that correlate with trained immunity, and elevated serum concentrations of the HNF1 target alpha-1 antitrypsin. Additionally, transcriptomic HSPC remodeling was epigenetically conveyed to peripheral CD14 monocytes, displaying an activated transcriptional signature three months after BCG vaccination. Taken together, transcriptomic, epigenomic, and functional reprogramming of HSPCs and peripheral monocytes is a hallmark of BCG-induced trained immunity in humans.

摘要

卡介苗（BCG）接种诱导的训练有素的免疫介导了有益的异源效应，但它的持久性和幅度的机制仍不清楚。在这项研究中，我们表明，BCG 疫苗接种在健康的人类志愿者中诱导骨髓中造血干细胞和祖细胞（HSPC）区室中与髓样细胞发育和功能相关的持久转录程序。我们确定了肝细胞核因子（HNF）家族成员 1a 和 b 是这种转录转变的关键调节因子。这些发现得到了以下证据的支持：BCG 接种婴儿的粒细胞数量增加，与训练有素的免疫相关的 HNF1 SNP 变体，以及 HNF1 靶标α-1 抗胰蛋白酶的血清浓度升高。此外，HSPC 的转录组重塑被表观遗传传递到外周 CD14 单核细胞，在 BCG 接种三个月后显示出激活的转录特征。总之，HSPC 和外周单核细胞的转录组、表观基因组和功能重编程是人类 BCG 诱导的训练有素的免疫的标志。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc4/7295478/dcf578e0145d/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc4/7295478/9ad3bdbd278a/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc4/7295478/13c58276928b/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc4/7295478/525e84028e68/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc4/7295478/f07e0cdc09cc/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc4/7295478/a1dbe4634f65/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc4/7295478/d5655687ec45/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc4/7295478/dcf578e0145d/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc4/7295478/9ad3bdbd278a/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc4/7295478/13c58276928b/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc4/7295478/525e84028e68/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc4/7295478/f07e0cdc09cc/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc4/7295478/a1dbe4634f65/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc4/7295478/d5655687ec45/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abc4/7295478/dcf578e0145d/gr6_lrg.jpg

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Dimensionality reduction for visualizing single-cell data using UMAP.使用UMAP进行单细胞数据可视化的降维方法。
Nat Biotechnol. 2018 Dec 3. doi: 10.1038/nbt.4314.
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Does BCG Vaccination Protect Against Nontuberculous Mycobacterial Infection? A Systematic Review and Meta-Analysis.BCG 疫苗接种是否可预防非结核分枝杆菌感染？系统评价和荟萃分析。
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