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Cell. 2018 Jan 11;172(1-2):147-161.e12. doi: 10.1016/j.cell.2017.11.034.

Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity.

Author information

1
Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany. Electronic address: ioannis.mitroulis@uniklinikum-dresden.de.
2
Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany.
3
Department of Microbiology, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, USA.
4
Paul Langerhans Institute Dresden, Helmholtz Zentrum München, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
5
DFG-Center for Regenerative Therapies Dresden, Dresden, Germany.
6
Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany; Paul Langerhans Institute Dresden, Helmholtz Zentrum München, University Hospital and Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
7
Myeloid Cell Biology, LIMES-Institute, University of Bonn, Bonn, Germany.
8
Department of Genomics and Immunoregulation, Life and Medical Science Institute, University of Bonn, Bonn, Germany; Molecular Immunology in Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
9
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA, Nijmegen, the Netherlands.
10
Institute of Clinical Chemistry and Pathobiochemistry, Otto von Guericke University, Magdeburg, Germany.
11
Deep Sequencing Group, Biotechnology Center, Technische Universität Dresden, Dresden, Germany.
12
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany; Lipotype GmbH, Dresden, Germany.
13
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
14
Department of Genomics and Immunoregulation, Life and Medical Science Institute, University of Bonn, Bonn, Germany; PRECISE - Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, Bonn, Germany.
15
Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
16
Department of Genomics and Immunoregulation, Life and Medical Science Institute, University of Bonn, Bonn, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA, Nijmegen, the Netherlands.
17
Institute of Clinical Chemistry and Laboratory Medicine, Technische Universität Dresden, Dresden, Germany. Electronic address: triantafyllos.chavakis@uniklinikum-dresden.de.

Abstract

Trained innate immunity fosters a sustained favorable response of myeloid cells to a secondary challenge, despite their short lifespan in circulation. We thus hypothesized that trained immunity acts via modulation of hematopoietic stem and progenitor cells (HSPCs). Administration of β-glucan (prototypical trained-immunity-inducing agonist) to mice induced expansion of progenitors of the myeloid lineage, which was associated with elevated signaling by innate immune mediators, such as IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF), and with adaptations in glucose metabolism and cholesterol biosynthesis. The trained-immunity-related increase in myelopoiesis resulted in a beneficial response to secondary LPS challenge and protection from chemotherapy-induced myelosuppression in mice. Therefore, modulation of myeloid progenitors in the bone marrow is an integral component of trained immunity, which to date, was considered to involve functional changes of mature myeloid cells in the periphery.

KEYWORDS:

GM-CSF; cholesterol biosynthesis; glycolysis; inflammation; innate immune memory; interleukin-1β; myelopoiesis; myelosuppression; trained innate immunity; β-glucan

PMID:
29328910
PMCID:
PMC5766828
DOI:
10.1016/j.cell.2017.11.034
[Indexed for MEDLINE]
Free PMC Article

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