Single-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective effects in circulating monocytes.
Single-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective effects in circulating monocytes.
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DOI：
10.1016/j.celrep.2021.110028
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发表时间：
2021-11-16
期刊：
影响因子：
8.8
通讯作者：
Xavier RJ
中科院分区：
文献类型：
--
作者：
Kong L;Moorlag SJCFM;Lefkovith A;Li B;Matzaraki V;van Emst L;Kang HA;Latorre I;Jaeger M;Joosten LAB;Netea MG;Xavier RJ
卡介苗是世界上使用最广泛的疫苗之一。除了预防结核病外，卡介苗还通过增强对异源病原体的二次免疫反应（称为“训练免疫”），对其他感染提供一定程度的非特异性保护。为了更好地了解卡介苗诱导的免疫重编程，我们使用细菌脂多糖（LPS）进行二次免疫刺激，在卡介苗接种前后进行单细胞转录组学测量。我们发现卡介苗可以减少全身炎症，并鉴定出75个与LPS反应改变的基因，包括炎症介质，如CCL3和CCL4，它们具有增强的反应。共表达分析显示，含有这些细胞因子的基因模块在卡介苗后失去了协调。其他模块表现出更强的协调性，包括我们确认在体外诱导训练免疫的几种人类核同种异构体。我们的研究结果将体内卡介苗给药与单细胞转录组变化联系起来，并在人类遗传学实验中得到验证，并突出了被认为负责卡介苗非特异性保护作用的基因。Kong等人利用单细胞转录组学研究了卡介苗接种后单核细胞免疫应答改变相关的基因表达变化。这组作者表明，卡介苗可以减少全身炎症，并鉴定出一组与疫苗的非特异性保护作用有关的基因。
Bacillus Calmette-Guérin (BCG) vaccine is one of the most widely used vaccines worldwide. In addition to protection against tuberculosis, BCG confers a degree of non-specific protection against other infections by enhancing secondary immune responses to heterologous pathogens, termed “trained immunity.” To better understand BCG-induced immune reprogramming, we perform single-cell transcriptomic measurements before and after BCG vaccination using secondary immune stimulation with bacterial lipopolysaccharide (LPS). We find that BCG reduces systemic inflammation and identify 75 genes with altered LPS responses, including inflammatory mediators such as CCL3 and CCL4 that have a heightened response. Co-expression analysis reveals that gene modules containing these cytokines lose coordination after BCG. Other modules exhibit increased coordination, including several humanin nuclear isoforms that we confirm induce trained immunity in vitro. Our results link in vivo BCG administration to single-cell transcriptomic changes, validated in human genetics experiments, and highlight genes that are putatively responsible for non-specific protective effects of BCG. Kong et al. use single-cell transcriptomics to characterize the gene expression changes involved in the altered immune response in monocytes after BCG vaccination. The authors show that BCG reduces systemic inflammation and identify a set of genes implicated in the vaccine’s non-specific protective effects.
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DOI：
10.1056/nejmoa1714021
发表时间：
2018-07-12
期刊：
The New England journal of medicine
影响因子：
--
作者：
Nemes E;Geldenhuys H;Rozot V;Rutkowski KT;Ratangee F;Bilek N;Mabwe S;Makhethe L;Erasmus M;Toefy A;Mulenga H;Hanekom WA;Self SG;Bekker LG;Ryall R;Gurunathan S;DiazGranados CA;Andersen P;Kromann I;Evans T;Ellis RD;Landry B;Hokey DA;Hopkins R;Ginsberg AM;Scriba TJ;Hatherill M;C-040-404 Study Team
通讯作者：
C-040-404 Study Team
DOI：
10.1093/bioinformatics/bts180
发表时间：
2012-06-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Shah TS;Liu JZ;Floyd JA;Morris JA;Wirth N;Barrett JC;Anderson CA
通讯作者：
Anderson CA
影响因子：
3.1
作者：
MATSUMOTO, K;OTANI, T;AZUMA, I
通讯作者：
AZUMA, I
影响因子：
4.7
作者：
Khurana N;Bhattacharyya S
通讯作者：
Bhattacharyya S
影响因子：
13.3
作者：
Netea-Maier RT;Plantinga TS;van de Veerdonk FL;Smit JW;Netea MG
通讯作者：
Netea MG