Cell Reports (May 2023)
A single-cell view on host immune transcriptional response to in vivo BCG-induced trained immunity
- Wenchao Li,
- Simone J.C.F.M. Moorlag,
- Valerie A.C.M. Koeken,
- Rutger J. Röring,
- L. Charlotte J. de Bree,
- Vera P. Mourits,
- Manoj K. Gupta,
- Bowen Zhang,
- Jianbo Fu,
- Zhenhua Zhang,
- Inge Grondman,
- Krista E. van Meijgaarden,
- Liang Zhou,
- Ahmed Alaswad,
- Leo A.B. Joosten,
- Reinout van Crevel,
- Cheng-Jian Xu,
- Mihai G. Netea,
- Yang Li
Affiliations
- Wenchao Li
- Department of Computational Biology of Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany
- Simone J.C.F.M. Moorlag
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
- Valerie A.C.M. Koeken
- Department of Computational Biology of Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
- Rutger J. Röring
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
- L. Charlotte J. de Bree
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
- Vera P. Mourits
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
- Manoj K. Gupta
- Department of Computational Biology of Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany
- Bowen Zhang
- Department of Computational Biology of Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany
- Jianbo Fu
- Department of Computational Biology of Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany
- Zhenhua Zhang
- Department of Computational Biology of Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany
- Inge Grondman
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
- Krista E. van Meijgaarden
- Department of Infectious Diseases, Leiden University Medical Center, Leiden, the Netherlands
- Liang Zhou
- Department of Computational Biology of Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany
- Ahmed Alaswad
- Department of Computational Biology of Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany
- Leo A.B. Joosten
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; Department of Medical Genetics, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Reinout van Crevel
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
- Cheng-Jian Xu
- Department of Computational Biology of Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
- Mihai G. Netea
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; Department for Genomics and Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany
- Yang Li
- Department of Computational Biology of Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany; TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Lower Saxony, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; Corresponding author
- Journal volume & issue
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Vol. 42,
no. 5
p. 112487
Abstract
Summary: Bacillus Calmette-Guérin (BCG) vaccination is a prototype model for the study of trained immunity (TI) in humans, and results in a more effective response of innate immune cells upon stimulation with heterologous stimuli. Here, we investigate the heterogeneity of TI induction by single-cell RNA sequencing of immune cells collected from 156 samples. We observe that both monocytes and CD8+ T cells show heterologous transcriptional responses to lipopolysaccharide, with an active crosstalk between these two cell types. Furthermore, the interferon-γ pathway is crucial in BCG-induced TI, and it is upregulated in functional high responders. Data-driven analyses and functional experiments reveal STAT1 to be one of the important transcription factors for TI shared in all identified monocyte subpopulations. Finally, we report the role of type I interferon-related and neutrophil-related TI transcriptional programs in patients with sepsis. These findings provide comprehensive insights into the importance of monocyte heterogeneity during TI in humans.
