Single-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective effects in circulating monocytes

Summary: 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 “train...

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Autores principales:	Lingjia Kong, Simone J.C.F.M. Moorlag, Ariel Lefkovith, Bihua Li, Vasiliki Matzaraki, Liesbeth van Emst, Heather A. Kang, Isabel Latorre, Martin Jaeger, Leo A.B. Joosten, Mihai G. Netea, Ramnik J. Xavier
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	BCG vaccination trained immunity monocytes cytokines single-cell sequencing humanin Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/d017840185dc456fa97a51273e8b4236
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spelling	oai:doaj.org-article:d017840185dc456fa97a51273e8b42362021-11-18T04:48:04ZSingle-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective effects in circulating monocytes2211-124710.1016/j.celrep.2021.110028https://doaj.org/article/d017840185dc456fa97a51273e8b42362021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721015102https://doaj.org/toc/2211-1247Summary: 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.Lingjia KongSimone J.C.F.M. MoorlagAriel LefkovithBihua LiVasiliki MatzarakiLiesbeth van EmstHeather A. KangIsabel LatorreMartin JaegerLeo A.B. JoostenMihai G. NeteaRamnik J. XavierElsevierarticleBCG vaccinationtrained immunitymonocytescytokinessingle-cell sequencinghumaninBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 7, Pp 110028- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	BCG vaccination trained immunity monocytes cytokines single-cell sequencing humanin Biology (General) QH301-705.5
spellingShingle	BCG vaccination trained immunity monocytes cytokines single-cell sequencing humanin Biology (General) QH301-705.5 Lingjia Kong Simone J.C.F.M. Moorlag Ariel Lefkovith Bihua Li Vasiliki Matzaraki Liesbeth van Emst Heather A. Kang Isabel Latorre Martin Jaeger Leo A.B. Joosten Mihai G. Netea Ramnik J. Xavier Single-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective effects in circulating monocytes
description	Summary: 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.
format	article
author	Lingjia Kong Simone J.C.F.M. Moorlag Ariel Lefkovith Bihua Li Vasiliki Matzaraki Liesbeth van Emst Heather A. Kang Isabel Latorre Martin Jaeger Leo A.B. Joosten Mihai G. Netea Ramnik J. Xavier
author_facet	Lingjia Kong Simone J.C.F.M. Moorlag Ariel Lefkovith Bihua Li Vasiliki Matzaraki Liesbeth van Emst Heather A. Kang Isabel Latorre Martin Jaeger Leo A.B. Joosten Mihai G. Netea Ramnik J. Xavier
author_sort	Lingjia Kong
title	Single-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective effects in circulating monocytes
title_short	Single-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective effects in circulating monocytes
title_full	Single-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective effects in circulating monocytes
title_fullStr	Single-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective effects in circulating monocytes
title_full_unstemmed	Single-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective effects in circulating monocytes
title_sort	single-cell transcriptomic profiles reveal changes associated with bcg-induced trained immunity and protective effects in circulating monocytes
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/d017840185dc456fa97a51273e8b4236
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Single-cell transcriptomic profiles reveal changes associated with BCG-induced trained immunity and protective effects in circulating monocytes

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