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MDSCs in infectious diseases: regulation, roles, and readjustment

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Abstract

Many pathogens, ranging from viruses to multicellular parasites, promote expansion of MDSCs, which are myeloid cells that exhibit immunosuppressive features. The roles of MDSCs in infection depend on the class and virulence mechanisms of the pathogen, the stage of the disease, and the pathology associated with the infection. This work compiles evidence supported by functional assays on the roles of different subsets of MDSCs in acute and chronic infections, including pathogen-associated malignancies, and discusses strategies to modulate MDSC dynamics to benefit the host.

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Abbreviations

Arg:

Arginase

Arm:

Armstrong

ATRA:

All-trans retinoic acid

B. fragilis :

Bacteroides fragilis

C. albicans :

Candida albicans

C13:

Clone 13

CCR:

C-C Chemokine receptor

COST:

European Cooperation in Science and Technology

EBV:

Epstein Barr virus

ETBF:

Enterotoxigenic Bacteroides fragilis

FV:

Friend virus

H. felis:

Helicobacter felis

H. polygyrus :

Heligmosomoides polygyrus

HbsAg:

HBV surface antigen

HDT:

Host-directed therapy

IAV:

Influenza A virus

iNKT:

Invariant NK T

JEV:

Japanese encephalitis virus

K. pneumoniae:

Klebsiella pneumoniae

L. major :

Leishmania major

LCMV:

Lymphocytic choriomeningitis virus

LOX:

Lipoxygenase

Mφ:

Macrophage

M-MDSC:

Monocytic MDSC

M. tuberculosis:

Mycobacterium tuberculosis

MR:

Mannose receptor

MRC:

Myeloid regulatory cell

mTOR:

Mammalian target of rapamycin

NADPH:

Nicotinamide adenine dinucleotide phosphate

NOS:

NO synthase

P. aeruginosa:

Pseudomonas aeruginosa

PcP:

Pneumocystis pneumonia

PDE:

Phosphodiesterase

PGE2:

Prostaglandin E2

PMN-MDSC:

Neutrophil-like MDSC

ROS:

Reactive oxygen species

S. aureus :

Staphylococcus aureus

SIV:

Simian immunodeficiency virus

T. crassiceps :

Taenia crassiceps

T. cruzi :

Trypanosoma cruzi

T. gondii :

Toxoplasma gondii

TB:

Tuberculosis

Tfh:

T Follicular helper

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Acknowledgements

We thank Ronnie Grant (University of Edinburgh) for figure editing.

Funding

This work was supported by European Cooperation in Science and Technology (COST) and the COST Action BM1404 Mye-EUNITER (http://www.mye-euniter.eu). COST is part of the European Union Framework Programme Horizon 2020. Estibaliz Glaría is supported by a fellowship from the University of Barcelona (Ajuts de Personal Investigador predoctoral en Formació, APIF); Thalia Garcia-Tellez is supported by the Institut Carnot Pasteur Maladie Infectieuses (ANR 11-CARN 017-01) as part of the Pasteur—Paris University (PPU) International PhD Program and by Sidaction.

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Authors and Affiliations

  1. Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493, Greifswald, Insel Riems, Germany

    Anca Dorhoi

  2. Faculty of Mathematics and Natural Sciences, University of Greifswald, Greifswald, Germany

    Anca Dorhoi

  3. Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany

    Anca Dorhoi & Natalie E. Nieuwenhuizen

  4. Nuclear Receptor Group, Department of Cell Biology, Physiology and Immunology, School of Biology, University of Barcelona, Av. Diagonal, 643, 3rd floor, 08028, Barcelona, Spain

    Estibaliz Glaría & Annabel F. Valledor

  5. Institute of Biomedicine of the University of Barcelona (IBUB), Barcelona, Spain

    Estibaliz Glaría & Annabel F. Valledor

  6. Institut Pasteur, HIV Inflammation and Persistence Unit, Paris, France

    Thalia Garcia-Tellez & Michaela Müller-Trutwin

  7. Institute of Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

    Gennadiy Zelinskyy

  8. Immunology of Viral Infections and Autoimmune Diseases (IMVA), IDMIT Department, CEA, Université Paris Sud 11, INSERM U1184, IBJF, Fontenay-aux-Roses, France

    Benoit Favier

  9. University Children’s Hospital and Interdisciplinary Center for Infectious Diseases, University of Tübingen, Tübingen, Germany

    Anurag Singh

  10. Department of Dermatology, University Hospital Münster, Münster, Germany

    Jan Ehrchen

  11. Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zurich, Switzerland

    Cornelia Gujer & Christian Münz

  12. i3S-Instituto de Investigação e Inovação em Saúde, Porto, Portugal

    Margarida Saraiva

  13. IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal

    Margarida Saraiva

  14. Molecular and Translational Cardiology, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany

    Yahya Sohrabi

  15. Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic

    Yahya Sohrabi

  16. Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal

    Ana E. Sousa

  17. Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Antwerp, Belgium

    Peter Delputte

Authors
  1. Anca Dorhoi
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  2. Estibaliz Glaría
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  3. Thalia Garcia-Tellez
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  4. Natalie E. Nieuwenhuizen
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  6. Benoit Favier
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  7. Anurag Singh
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  9. Cornelia Gujer
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  15. Michaela Müller-Trutwin
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  16. Annabel F. Valledor
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Contributions

Conceptualization and writing of the original draft: all authors. Figure design: AD, EG, TG-T, and AFV. Revisions and editing: AD, NEN, CG, and AFV. Supervision: AD and AFV. All authors approved the final version of this paper.

Corresponding authors

Correspondence to Anca Dorhoi or Annabel F. Valledor.

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The authors declare that they have no conflicts of interest.

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Dorhoi, A., Glaría, E., Garcia-Tellez, T. et al. MDSCs in infectious diseases: regulation, roles, and readjustment. Cancer Immunol Immunother 68, 673–685 (2019). https://doi.org/10.1007/s00262-018-2277-y

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  • DOI: https://doi.org/10.1007/s00262-018-2277-y

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