Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity

被引：844

作者：

Mitroulis, Ioannis ^{[1
,19
,20
]}

Ruppova, Klara ^{[1
]}

Wang, Baomei ^{[2
]}

Chen, Lan-Sun ^{[1
]}

Grzybek, Michal ^{[3
,4
,5
]}

Grinenko, Tatyana ^{[1
]}

Eugster, Anne ^{[6
]}

Troullinaki, Maria ^{[1
]}

Palladini, Alessandra ^{[1
,3
,4
,5
]}

Kourtzelis, Ioannis ^{[1
]}

Chatzigeorgiou, Antonios ^{[1
]}

Schlitzer, Andreas ^{[7
]}

Beyer, Marc ^{[8
,9
]}

Joosten, Leo A. B. ^{[10
,11
]}

Isermann, Berend ^{[12
]}

Lesche, Mathias ^{[13
]}

Petzold, Andreas ^{[13
]}

Simons, Kai ^{[14
,15
]}

Henry, Ian ^{[14
]}

Dahl, Andreas ^{[13
]}

Schultze, Joachim L. ^{[16
,17
]}

Wielockx, Ben ^{[1
]}

Zamboni, Nicola ^{[18
]}

Mirtschink, Peter ^{[1
]}

Coskun, Unal ^{[3
,4
,5
]}

Hajishengallis, George ^{[2
]}

Netea, Mihai G. ^{[8
,10
,11
]}

Chavakis, Triantafyllos ^{[1
]}

机构：

[1] Tech Univ Dresden, Inst Clin Chem & Lab Med, Dresden, Germany

[2] Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA

[3] Tech Univ Dresden, Univ Hosp, Helmholtz Zentrum Munchen, Paul Langerhans Inst Dresden, Dresden, Germany

[4] Tech Univ Dresden, Fac Med Carl Gustav Carus, Dresden, Germany

[5] German Ctr Diabet Res DZD eV, Neuherberg, Germany

[6] DFG Ctr Regenerat Therapies Dresden, Dresden, Germany

[7] Univ Bonn, LIMES Inst, Myeloid Cell Biol, Bonn, Germany

[8] Univ Bonn, Life & Med Sci Inst, Dept Genom & Immunoregulat, Bonn, Germany

[9] German Ctr Neurodegenerat Dis DZNE, Mol Immunol Neurodegenerat, Bonn, Germany

[10] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 GA Nijmegen, Netherlands

[11] Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, NL-6525 GA Nijmegen, Netherlands

[12] Otto Von Guericke Univ, Inst Clin Chem & Pathobiochem, Magdeburg, Germany

[13] Tech Univ Dresden, Deep Sequencing Grp, Biotechnol Ctr, Dresden, Germany

[14] Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany

[15] Lipotype GmbH, Dresden, Germany

[16] German Ctr Neurodegenerat Dis, PRECISE Platform Single Cell Genom & Epigenom, Bonn, Germany

[17] Univ Bonn, Bonn, Germany

[18] Swiss Fed Inst Technol, Inst Mol Syst Biol, Zurich, Switzerland

[19] Tech Univ Dresden, Inst Clin Chem & Lab Med, Dresden, Germany

[20] Natl Ctr Tumor Dis, Dresden, Germany

来源：

CELL | 2018年 / 172卷 / 1-2期

关键词：

HEMATOPOIETIC STEM-CELLS; HIGH-THROUGHPUT; SELF-RENEWAL; LINEAGE COMMITMENT; GLOBAL ANALYSIS; DORMANCY; DIFFERENTIATION; PROLIFERATION; ACCUMULATION; QUIESCENCE;

D O I：

10.1016/j.cell.2017.11.034

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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 beta-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-1 beta 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.

引用

页码：147 / +

页数：27

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