MMR vaccination induces a trained immunity program characterized by functional and metabolic reprogramming of γδ T cells
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Abstract The measles, mumps and rubella (MMR) vaccine protects against all-cause mortality in children, but the immunological mechanisms mediating these effects are poorly known. We systematically investigated whether MMR can induce long-term functional changes in innate immune cells, a process termed trained immunity, that could at least partially mediate this heterologous protection. In a randomized placebo-controlled trial, 39 healthy adults received either the MMR vaccine or a placebo. By using single-cell RNA-sequencing, we found that MMR caused transcriptomic changes in CD14-positive monocytes and NK cells, but most profoundly in γδ T cells. Surprisingly, monocyte function was not altered by MMR vaccination. In contrast, the function of γδ T cells was significantly enhanced by MMR vaccination, with higher production of TNF and IFNγ, as well as upregulation of cellular metabolic pathways. In conclusion, we describe a new trained immunity program characterized by modulation of γδ T cell function induced by MMR vaccination. One-sentence summary MMR vaccination induces cellular and metabolic reprogramming in γδ T cells towards a more active phenotype.
Authors 25
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Radboud University Nijmegen · Radboud University Medical Center · Radboud Institute for Molecular Life Sciences
Affiliation as printed
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
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Radboud University Nijmegen · Radboud University Medical Center · Radboud Institute for Molecular Life Sciences
Affiliation as printed
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
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Radboud University Nijmegen · Radboud University Medical Center · Medizinische Hochschule Hannover · Radboud Institute for Molecular Life Sciences · Helmholtz Centre for Infection Research · Centre for Individualised Infection Medicine · Center for Experimental and Clinical Infection Research
Affiliation as printed
Department of Computational Biology for Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany
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Affiliation as printed
Department of Immunology and Metabolism, Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany
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Radboud University Nijmegen · Radboud University Medical Center · Radboud Institute for Molecular Life Sciences
Affiliation as printed
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
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Radboud University Nijmegen · Radboud University Medical Center · Radboud Institute for Molecular Life Sciences
Affiliation as printed
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
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Radboud University Nijmegen · Radboud University Medical Center · Medizinische Hochschule Hannover · Radboud Institute for Molecular Life Sciences · Helmholtz Centre for Infection Research · Centre for Individualised Infection Medicine · Center for Experimental and Clinical Infection Research
Affiliation as printed
Department of Computational Biology for Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany
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Radboud University Nijmegen · Radboud University Medical Center
Affiliation as printed
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
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Radboud University Nijmegen · Radboud University Medical Center · Radboud Institute for Molecular Life Sciences
Affiliation as printed
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
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Radboud University Nijmegen · Radboud University Medical Center · Radboud Institute for Molecular Life Sciences
Affiliation as printed
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
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Radboud University Nijmegen · Radboud University Medical Center · Radboud Institute for Molecular Life Sciences
Affiliation as printed
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
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Düsseldorf University Hospital · Heinrich Heine University Düsseldorf
Affiliation as printed
Department for Pediatric Oncology, Hematology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University Duesseldorf, Dusseldorf
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Düsseldorf University Hospital · Heinrich Heine University Düsseldorf
Affiliation as printed
Department for Pediatric Oncology, Hematology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University Duesseldorf, Dusseldorf
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Düsseldorf University Hospital · Heinrich Heine University Düsseldorf
Affiliation as printed
Institute of Virology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University Duesseldorf, Dusseldorf, Germany
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Düsseldorf University Hospital · Heinrich Heine University Düsseldorf
Affiliation as printed
Institute of Virology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University Duesseldorf, Dusseldorf, Germany
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Düsseldorf University Hospital · Heinrich Heine University Düsseldorf
Affiliation as printed
Institute of Virology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University Duesseldorf, Dusseldorf, Germany
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Düsseldorf University Hospital · Heinrich Heine University Düsseldorf
Affiliation as printed
Institute of Virology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University Duesseldorf, Dusseldorf, Germany
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Düsseldorf University Hospital · Heinrich Heine University Düsseldorf
Affiliation as printed
Department for Pediatric Oncology, Hematology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Heinrich Heine University Duesseldorf, Dusseldorf
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Leiden University Medical Center
Affiliation as printed
Leiden Genome Technology Center, Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Leiden Genome Technology Center, Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
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Leiden University Medical Center
Affiliation as printed
Leiden Genome Technology Center, Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
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Radboud University Nijmegen · Radboud University Medical Center · Radboud Institute for Molecular Life Sciences
Affiliation as printed
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
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Medizinische Hochschule Hannover · Helmholtz Centre for Infection Research · Center for Experimental and Clinical Infection Research
Affiliation as printed
TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany
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Radboud University Nijmegen · Radboud University Medical Center · Medizinische Hochschule Hannover · Radboud Institute for Molecular Life Sciences · Helmholtz Centre for Infection Research · Centre for Individualised Infection Medicine · Center for Experimental and Clinical Infection Research
Affiliation as printed
Department of Computational Biology for Individualised Medicine, Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany
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Mihai Gheorghe Netea corresponding
University of Bonn · Radboud University Nijmegen · Radboud University Medical Center · Radboud Institute for Molecular Life Sciences
Affiliation as printed
Department of Immunology and Metabolism, Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud university medical center, Nijmegen, The Netherlands
Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands
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