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

Cell Reports

Heather A. Kang¹  Simone J.C.F.M. Moorlag¹  Leo A.B. Joosten²  Bihua Li²  Mihai G. Netea³  Lingjia Kong³  Vasiliki Matzaraki³  Liesbeth van Emst³  Ramnik J. Xavier⁴  Ariel Lefkovith⁵  Martin Jaeger⁵  Isabel Latorre⁵ 

[1] Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA;Radboud Center for Infectious Diseases, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands;Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;Center for Computational and Integrative Biology and Department of Molecular Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA;Department of Internal Medicine, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands;

关键词: BCG vaccination;    trained immunity;    monocytes;    cytokines;    single-cell sequencing;    humanin;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown