Advertisement

Cancer Immunology, Immunotherapy

, Volume 68, Issue 4, pp 673–685 | Cite as

MDSCs in infectious diseases: regulation, roles, and readjustment

  • Anca DorhoiEmail author
  • Estibaliz Glaría
  • Thalia Garcia-Tellez
  • Natalie E. Nieuwenhuizen
  • Gennadiy Zelinskyy
  • Benoit Favier
  • Anurag Singh
  • Jan Ehrchen
  • Cornelia Gujer
  • Christian Münz
  • Margarida Saraiva
  • Yahya Sohrabi
  • Ana E. Sousa
  • Peter Delputte
  • Michaela Müller-Trutwin
  • Annabel F. ValledorEmail author
Symposium-in-Writing Paper

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.

Keywords

Myeloid regulatory cells MDSC Infection Immunosuppression Oncogenic viruses Mye-EUNITER 

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

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

Notes

Acknowledgements

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

Author 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.

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

262_2018_2277_MOESM1_ESM.pdf (143 kb)
Supplementary material 1 (PDF 144 KB)

References

  1. 1.
    Bronte V, Brandau S, Chen S-H et al (2016) Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun 7:12150.  https://doi.org/10.1038/ncomms12150 CrossRefGoogle Scholar
  2. 2.
    Bruger AM, Dorhoi A, Esendagli G et al (2018) How to measure the immunosuppressive activity of MDSC: assays, problems and potential solutions. Cancer Immunol Immunother.  https://doi.org/10.1007/s00262-018-2170-8 Google Scholar
  3. 3.
    Skabytska Y, Wölbing F, Günther C et al (2014) Cutaneous innate immune sensing of toll-like receptor 2–6 ligands suppresses T cell immunity by inducing myeloid-derived suppressor cells. Immunity 41:762–775.  https://doi.org/10.1016/J.IMMUNI.2014.10.009 CrossRefGoogle Scholar
  4. 4.
    Arora M, Poe SL, Oriss TB et al (2010) TLR4/MyD88-induced CD11b+ Gr-1 int F4/80+ non-migratory myeloid cells suppress Th2 effector function in the lung. Mucosal Immunol 3:578–593.  https://doi.org/10.1038/mi.2010.41 CrossRefGoogle Scholar
  5. 5.
    Rieber N, Brand A, Hector A et al (2013) Flagellin induces myeloid-derived suppressor cells: implications for Pseudomonas aeruginosa infection in cystic fibrosis lung disease. J Immunol 190:1276–1284.  https://doi.org/10.4049/jimmunol.1202144 CrossRefGoogle Scholar
  6. 6.
    Ren JP, Zhao J, Dai J et al (2016) Hepatitis C virus-induced myeloid-derived suppressor cells regulate T-cell differentiation and function via the signal transducer and activator of transcription 3 pathway. Immunology 148:377–386.  https://doi.org/10.1111/imm.12616 CrossRefGoogle Scholar
  7. 7.
    Zhai N, Li H, Song H et al (2017) Hepatitis C virus induces MDSCs-like monocytes through TLR2/PI3K/AKT/STAT3 signaling. PLoS One 12:e0170516.  https://doi.org/10.1371/journal.pone.0170516 CrossRefGoogle Scholar
  8. 8.
    Tacke RS, Lee H-C, Goh C et al (2012) Myeloid suppressor cells induced by hepatitis C virus suppress T-cell responses through the production of reactive oxygen species. Hepatology 55:343–353.  https://doi.org/10.1002/hep.24700 CrossRefGoogle Scholar
  9. 9.
    Goh CC, Roggerson KM, Lee H-C et al (2016) Hepatitis C virus-induced myeloid-derived suppressor cells suppress NK cell IFN-γ production by altering cellular metabolism via arginase-1. J Immunol 196:2283–2292.  https://doi.org/10.4049/jimmunol.1501881 CrossRefGoogle Scholar
  10. 10.
    Fang Z, Li J, Yu X et al (2015) Polarization of monocytic myeloid-derived suppressor cells by hepatitis B surface antigen is mediated via ERK/IL-6/STAT3 signaling feedback and restrains the activation of T cells in chronic hepatitis B virus infection. J Immunol 195:4873–4883.  https://doi.org/10.4049/jimmunol.1501362 CrossRefGoogle Scholar
  11. 11.
    Garg A, Spector SA (2014) HIV type 1 gp120-induced expansion of myeloid derived suppressor cells is dependent on interleukin 6 and suppresses immunity. J Infect Dis 209:441–451.  https://doi.org/10.1093/infdis/jit469 CrossRefGoogle Scholar
  12. 12.
    Dorhoi A, Du Plessis N (2018) Monocytic myeloid-derived suppressor cells in chronic infections. Front Immunol 8:1895.  https://doi.org/10.3389/fimmu.2017.01895 CrossRefGoogle Scholar
  13. 13.
    De Santo C, Salio M, Masri SH et al (2008) Invariant NKT cells reduce the immunosuppressive activity of influenza A virus-induced myeloid-derived suppressor cells in mice and humans. J Clin Invest 118:4036–4048.  https://doi.org/10.1172/JCI36264 CrossRefGoogle Scholar
  14. 14.
    Jeisy-Scott V, Davis WG, Patel JR et al (2011) Increased MDSC accumulation and Th2 biased response to influenza A virus infection in the absence of TLR7 in mice. PLoS One 6:e25242.  https://doi.org/10.1371/journal.pone.0025242 CrossRefGoogle Scholar
  15. 15.
    Rieber N, Singh A, Öz H et al (2015) Pathogenic fungi regulate immunity by inducing neutrophilic myeloid-derived suppressor cells. Cell Host Microbe 17:507–514.  https://doi.org/10.1016/j.chom.2015.02.007 CrossRefGoogle Scholar
  16. 16.
    Albeituni SH, Ding C, Liu M et al (2016) Yeast-derived particulate β-glucan treatment subverts the suppression of myeloid-derived suppressor cells (MDSC) by inducing polymorphonuclear MDSC apoptosis and monocytic MDSC differentiation to APC in cancer. J Immunol 196:2167–2180.  https://doi.org/10.4049/jimmunol.1501853 CrossRefGoogle Scholar
  17. 17.
    Gomez-Garcia L, Lopez-Marin LM, Saavedra R et al (2005) Intact glycans from cestode antigens are involved in innate activation of myeloid suppressor cells. Parasite Immunol 27:395–405.  https://doi.org/10.1111/j.1365-3024.2005.00790.x CrossRefGoogle Scholar
  18. 18.
    Terrazas LI, Walsh KL, Piskorska D et al (2001) The schistosome oligosaccharide lacto-N-neotetraose expands Gr1(+) cells that secrete anti-inflammatory cytokines and inhibit proliferation of naive CD4(+) cells: a potential mechanism for immune polarization in helminth infections. J Immunol 167:5294–5303CrossRefGoogle Scholar
  19. 19.
    Atochina O, Daly-Engel T, Piskorska D et al (2001) A schistosome-expressed immunomodulatory glycoconjugate expands peritoneal Gr1(+) macrophages that suppress naive CD4(+) T cell proliferation via an IFN-gamma and nitric oxide-dependent mechanism. J Immunol 167:4293–4302CrossRefGoogle Scholar
  20. 20.
    Wagner A, Schabussova I, Drinic M et al (2016) Oocyst-derived extract of Toxoplasma gondii serves as potent immunomodulator in a mouse model of birch pollen allergy. PLoS One 11:e0155081.  https://doi.org/10.1371/journal.pone.0155081 CrossRefGoogle Scholar
  21. 21.
    Ost M, Singh A, Peschel A et al (2016) Myeloid-derived suppressor cells in bacterial infections. Front Cell Infect Microbiol 6:37.  https://doi.org/10.3389/fcimb.2016.00037 CrossRefGoogle Scholar
  22. 22.
    Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9:162–174.  https://doi.org/10.1038/nri2506 CrossRefGoogle Scholar
  23. 23.
    Veglia F, Perego M, Gabrilovich D (2018) Myeloid-derived suppressor cells coming of age. Nat Immunol 19:108–119.  https://doi.org/10.1038/s41590-017-0022-x CrossRefGoogle Scholar
  24. 24.
    Arocena AR, Onofrio LI, Pellegrini AV et al (2014) Myeloid-derived suppressor cells are key players in the resolution of inflammation during a model of acute infection. Eur J Immunol 44:184–194.  https://doi.org/10.1002/eji.201343606 CrossRefGoogle Scholar
  25. 25.
    Sander LE, Sackett SD, Dierssen U et al (2010) Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function. J Exp Med 207:1453–1464.  https://doi.org/10.1084/jem.20091474 CrossRefGoogle Scholar
  26. 26.
    Ribechini E, Hutchinson JA, Hergovits S et al (2017) Novel GM-CSF signals via IFN-γR/IRF-1 and AKT/mTOR license monocytes for suppressor function. Blood Adv 1:947–960.  https://doi.org/10.1182/bloodadvances.2017006858 Google Scholar
  27. 27.
    Haverkamp JM, Smith AM, Weinlich R et al (2014) Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways. Immunity 41:947–959.  https://doi.org/10.1016/j.immuni.2014.10.020 CrossRefGoogle Scholar
  28. 28.
    Wang C, Zhang N, Qi L et al (2017) Myeloid-derived suppressor cells inhibit T follicular helper cell immune response in japanese encephalitis virus infection. J Immunol 199:3094–3105.  https://doi.org/10.4049/jimmunol.1700671 CrossRefGoogle Scholar
  29. 29.
    Drabczyk-Pluta M, Werner T, Hoffmann D et al (2017) Granulocytic myeloid-derived suppressor cells suppress virus-specific CD8+ T cell responses during acute friend retrovirus infection. Retrovirology 14:42.  https://doi.org/10.1186/s12977-017-0364-3 CrossRefGoogle Scholar
  30. 30.
    Voisin M-B, Buzoni-Gatel D, Bout D, Velge-Roussel F (2004) Both expansion of regulatory GR1+ CD11b+ myeloid cells and anergy of T lymphocytes participate in hyporesponsiveness of the lung-associated immune system during acute toxoplasmosis. Infect Immun 72:5487–5492.  https://doi.org/10.1128/IAI.72.9.5487-5492.2004 CrossRefGoogle Scholar
  31. 31.
    Darcy CJ, Minigo G, Piera KA et al (2014) Neutrophils with myeloid derived suppressor function deplete arginine and constrain T cell function in septic shock patients. Crit Care 18:R163.  https://doi.org/10.1186/cc14003 CrossRefGoogle Scholar
  32. 32.
    Janols H, Bergenfelz C, Allaoui R et al (2014) A high frequency of MDSCs in sepsis patients, with the granulocytic subtype dominating in Gram-positive cases. J Leukoc Biol 96:685–693.  https://doi.org/10.1189/jlb.5HI0214-074R CrossRefGoogle Scholar
  33. 33.
    Uhel F, Azzaoui I, Grégoire M et al (2017) Early expansion of circulating granulocytic myeloid-derived suppressor cells predicts development of nosocomial infections in patients with sepsis. Am J Respir Crit Care Med 196:315–327.  https://doi.org/10.1164/rccm.201606-1143OC CrossRefGoogle Scholar
  34. 34.
    Delano MJ, Scumpia PO, Weinstein JS et al (2007) MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis. J Exp Med 204:1463–1474.  https://doi.org/10.1084/jem.20062602 CrossRefGoogle Scholar
  35. 35.
    Poe SL, Arora M, Oriss TB et al (2013) STAT1-regulated lung MDSC-like cells produce IL-10 and efferocytose apoptotic neutrophils with relevance in resolution of bacterial pneumonia. Mucosal Immunol 6:189–199.  https://doi.org/10.1038/mi.2012.62 CrossRefGoogle Scholar
  36. 36.
    Cuervo H, Guerrero NA, Carbajosa S et al (2011) Myeloid-derived suppressor cells infiltrate the heart in acute Trypanosoma cruzi infection. J Immunol 187:2656–2665.  https://doi.org/10.4049/jimmunol.1002928 CrossRefGoogle Scholar
  37. 37.
    Sanmarco LM, Visconti LM, Eberhardt N et al (2016) IL-6 improves the nitric oxide-induced cytotoxic CD8+ T cell dysfunction in human chagas disease. Front Immunol 7:626.  https://doi.org/10.3389/fimmu.2016.00626 CrossRefGoogle Scholar
  38. 38.
    Nathan C, Ding A (2010) Nonresolving Inflammation. Cell 140:871–882.  https://doi.org/10.1016/j.cell.2010.02.029 CrossRefGoogle Scholar
  39. 39.
    White MK, Pagano JS, Khalili K (2014) Viruses and human cancers: a long road of discovery of molecular paradigms. Clin Microbiol Rev 27:463–481.  https://doi.org/10.1128/CMR.00124-13 CrossRefGoogle Scholar
  40. 40.
    Chang AH, Parsonnet J (2010) Role of bacteria in oncogenesis. Clin Microbiol Rev 23:837–857.  https://doi.org/10.1128/CMR.00012-10 CrossRefGoogle Scholar
  41. 41.
    van Tong H, Brindley PJ, Meyer CG, Velavan TP (2017) Parasite infection, carcinogenesis and human malignancy. EBioMedicine 15:12–23.  https://doi.org/10.1016/j.ebiom.2016.11.034 CrossRefGoogle Scholar
  42. 42.
    Yang B, Wang X, Jiang J et al (2014) Identification of CD244-expressing myeloid-derived suppressor cells in patients with active tuberculosis. Immunol Lett 158:66–72.  https://doi.org/10.1016/j.imlet.2013.12.003 CrossRefGoogle Scholar
  43. 43.
    du Plessis N, Loebenberg L, Kriel M et al (2013) Increased frequency of myeloid-derived suppressor cells during active tuberculosis and after recent Mycobacterium tuberculosis infection suppresses T-cell function. Am J Respir Crit Care Med 188:724–732.  https://doi.org/10.1164/rccm.201302-0249OC CrossRefGoogle Scholar
  44. 44.
    El Daker S, Sacchi A, Tempestilli M et al (2015) Granulocytic myeloid derived suppressor cells expansion during active pulmonary tuberculosis is associated with high nitric oxide plasma level. PLoS One 10:e0123772.  https://doi.org/10.1371/journal.pone.0123772 CrossRefGoogle Scholar
  45. 45.
    Knaul JK, Jörg S, Oberbeck-Mueller D et al (2014) Lung-residing myeloid-derived suppressors display dual functionality in murine pulmonary tuberculosis. Am J Respir Crit Care Med 190:1053–1066.  https://doi.org/10.1164/rccm.201405-0828OC CrossRefGoogle Scholar
  46. 46.
    Tsiganov EN, Verbina EM, Radaeva TV et al (2014) Gr-1dimCD11b+ immature myeloid-derived suppressor cells but not neutrophils are markers of lethal tuberculosis infection in mice. J Immunol 192:4718–4727.  https://doi.org/10.4049/jimmunol.1301365 CrossRefGoogle Scholar
  47. 47.
    Gupta S, Cheung L, Pokkali S et al (2017) Suppressor cell-depleting immunotherapy with denileukin diftitox is an effective host-directed therapy for tuberculosis. J Infect Dis 215:1883–1887.  https://doi.org/10.1093/infdis/jix208 CrossRefGoogle Scholar
  48. 48.
    Heim CE, Vidlak D, Scherr TD et al (2014) Myeloid-derived suppressor cells contribute to Staphylococcus aureus orthopedic biofilm infection. J Immunol 192:3778–3792.  https://doi.org/10.4049/jimmunol.1303408 CrossRefGoogle Scholar
  49. 49.
    Ding L, Hayes MM, Photenhauer A et al (2016) Schlafen 4–expressing myeloid-derived suppressor cells are induced during murine gastric metaplasia. J Clin Invest 126:2867–2880.  https://doi.org/10.1172/JCI82529 CrossRefGoogle Scholar
  50. 50.
    Thiele Orberg E, Fan H, Tam AJ et al (2017) The myeloid immune signature of enterotoxigenic Bacteroides fragilis-induced murine colon tumorigenesis. Mucosal Immunol 10:421–433.  https://doi.org/10.1038/mi.2016.53 CrossRefGoogle Scholar
  51. 51.
    Norris BA, Uebelhoer LS, Nakaya HI et al (2013) Chronic but not acute virus infection induces sustained expansion of myeloid suppressor cell numbers that inhibit viral-specific T cell immunity. Immunity 38:309–321.  https://doi.org/10.1016/j.immuni.2012.10.022 CrossRefGoogle Scholar
  52. 52.
    Green KA, Cook WJ, Green WR (2013) Myeloid-derived suppressor cells in murine retrovirus-induced AIDS inhibit T- and B-cell responses in vitro that are used to define the immunodeficiency. J Virol 87:2058–2071.  https://doi.org/10.1128/JVI.01547-12 CrossRefGoogle Scholar
  53. 53.
    Alaoui L, Palomino G, Zurawski S et al (2017) Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs. Cell Mol Life Sci 1–17.  https://doi.org/10.1007/s00018-017-2712-9
  54. 54.
    Huot N, Rascle P, Garcia-Tellez T et al (2016) Innate immune cell responses in non pathogenic versus pathogenic SIV infections. Curr Opin Virol 19:37–44.  https://doi.org/10.1016/j.coviro.2016.06.011 CrossRefGoogle Scholar
  55. 55.
    Zhang Z-N, Yi N, Zhang T-W et al (2017) Myeloid-derived suppressor cells associated with disease progression in primary HIV infection. JAIDS J Acquir Immune Defic Syndr 76:200–208.  https://doi.org/10.1097/QAI.0000000000001471 CrossRefGoogle Scholar
  56. 56.
    Vollbrecht T, Stirner R, Tufman A et al (2012) Chronic progressive HIV-1 infection is associated with elevated levels of myeloid-derived suppressor cells. AIDS 26:F31–F37.  https://doi.org/10.1097/QAD.0b013e328354b43f CrossRefGoogle Scholar
  57. 57.
    Tumino N, Turchi F, Meschi S et al (2015) In HIV-positive patients, myeloid-derived suppressor cells induce T-cell anergy by suppressing CD3 ζ expression through ELF-1 inhibition. AIDS 29:2397–2407.  https://doi.org/10.1097/QAD.0000000000000871 CrossRefGoogle Scholar
  58. 58.
    Qin A, Cai W, Pan T et al (2013) Expansion of monocytic myeloid-derived suppressor cells dampens T cell function in HIV-1-seropositive individuals. J Virol 87:1477–1490.  https://doi.org/10.1128/JVI.01759-12 CrossRefGoogle Scholar
  59. 59.
    Gama L, Shirk EN, Russell JN et al (2012) Expansion of a subset of CD14highCD16negCCR2low/neg monocytes functionally similar to myeloid-derived suppressor cells during SIV and HIV infection. J Leukoc Biol 91:803–816.  https://doi.org/10.1189/jlb.1111579 CrossRefGoogle Scholar
  60. 60.
    Dross SE, Munson PV, Kim SE et al (2017) Kinetics of myeloid-derived suppressor cell frequency and function during simian immunodeficiency virus infection, combination antiretroviral therapy, and treatment interruption. J Immunol 198:757–766.  https://doi.org/10.4049/jimmunol.1600759 CrossRefGoogle Scholar
  61. 61.
    Cai W, Qin A, Guo P et al (2013) Clinical significance and functional studies of myeloid-derived suppressor cells in chronic hepatitis C patients. J Clin Immunol 33:798–808.  https://doi.org/10.1007/s10875-012-9861-2 CrossRefGoogle Scholar
  62. 62.
    Zeng Q-L, Yang B, Sun H-Q et al (2014) Myeloid-derived suppressor cells are associated with viral persistence and downregulation of TCR ζ chain expression on CD8(+) T cells in chronic hepatitis C patients. Mol Cells 37:66–73.  https://doi.org/10.14348/molcells.2014.2282 CrossRefGoogle Scholar
  63. 63.
    Nonnenmann J, Stirner R, Roider J et al (2014) Lack of significant elevation of myeloid-derived suppressor cells in peripheral blood of chronically hepatitis C virus-infected individuals. J Virol 88:7678–7682.  https://doi.org/10.1128/JVI.00113-14 CrossRefGoogle Scholar
  64. 64.
    Huang A, Zhang B, Yan W et al (2014) Myeloid-derived suppressor cells regulate immune response in patients with chronic hepatitis B virus infection through PD-1-induced IL-10. J Immunol 193:5461–5469.  https://doi.org/10.4049/jimmunol.1400849 CrossRefGoogle Scholar
  65. 65.
    Chen S, Akbar SMF, Abe M et al (2011) Immunosuppressive functions of hepatic myeloid-derived suppressor cells of normal mice and in a murine model of chronic hepatitis B virus. Clin Exp Immunol 166:134–142.  https://doi.org/10.1111/j.1365-2249.2011.04445.x CrossRefGoogle Scholar
  66. 66.
    Kong X, Sun R, Chen Y et al (2014) γδT cells drive myeloid-derived suppressor cell-mediated CD8+ T cell exhaustion in hepatitis B virus-induced immunotolerance. J Immunol 193:1645–1653.  https://doi.org/10.4049/jimmunol.1303432 CrossRefGoogle Scholar
  67. 67.
    Pallett LJ, Gill US, Quaglia A et al (2015) Metabolic regulation of hepatitis B immunopathology by myeloid-derived suppressor cells. Nat Med 21:591–600.  https://doi.org/10.1038/nm.3856 CrossRefGoogle Scholar
  68. 68.
    Cesarman E (2014) Gammaherpesviruses and lymphoproliferative disorders. Annu Rev Pathol Mech Dis 9:349–372.  https://doi.org/10.1146/annurev-pathol-012513-104656 CrossRefGoogle Scholar
  69. 69.
    Romano A, Parrinello NL, Vetro C et al (2015) Circulating myeloid-derived suppressor cells correlate with clinical outcome in Hodgkin Lymphoma patients treated up-front with a risk-adapted strategy. Br J Haematol 168:689–700.  https://doi.org/10.1111/bjh.13198 CrossRefGoogle Scholar
  70. 70.
    Zhang H, Li Z-L, Ye S-B et al (2015) Myeloid-derived suppressor cells inhibit T cell proliferation in human extranodal NK/T cell lymphoma: a novel prognostic indicator. Cancer Immunol Immunother 64:1587–1599.  https://doi.org/10.1007/s00262-015-1765-6 CrossRefGoogle Scholar
  71. 71.
    Cai T-T, Ye S-B, Liu Y-N et al (2017) LMP1-mediated glycolysis induces myeloid-derived suppressor cell expansion in nasopharyngeal carcinoma. PLOS Pathog 13:e1006503.  https://doi.org/10.1371/journal.ppat.1006503 CrossRefGoogle Scholar
  72. 72.
    Maizels RM, McSorley HJ (2016) Regulation of the host immune system by helminth parasites. J Allergy Clin Immunol 138:666–675.  https://doi.org/10.1016/j.jaci.2016.07.007 CrossRefGoogle Scholar
  73. 73.
    Yang Q, Qiu H, Xie H et al (2017) A Schistosoma japonicum infection promotes the expansion of myeloid-derived suppressor cells by activating the JAK/STAT3 pathway. J Immunol 198:4716–4727.  https://doi.org/10.4049/jimmunol.1601860 CrossRefGoogle Scholar
  74. 74.
    Valanparambil RM, Tam M, Jardim A et al (2017) Primary Heligmosomoides polygyrus bakeri infection induces myeloid-derived suppressor cells that suppress CD4+ Th2 responses and promote chronic infection. Mucosal Immunol 10:238–249.  https://doi.org/10.1038/mi.2016.36 CrossRefGoogle Scholar
  75. 75.
    Van Ginderachter JA, Beschin A, De Baetselier P, Raes G (2010) Myeloid-derived suppressor cells in parasitic infections. Eur J Immunol 40:2976–2985.  https://doi.org/10.1002/eji.201040911 CrossRefGoogle Scholar
  76. 76.
    Brys L, Beschin A, Raes G et al (2005) Reactive oxygen species and 12/15-lipoxygenase contribute to the antiproliferative capacity of alternatively activated myeloid cells elicited during helminth infection. J Immunol 174:6095–6104.  https://doi.org/10.4049/jimmunol.174.10.6095 CrossRefGoogle Scholar
  77. 77.
    Pereira WF, Ribeiro-Gomes FL, Guillermo LVC et al (2011) Myeloid-derived suppressor cells help protective immunity to Leishmania major infection despite suppressed T cell responses. J Leukoc Biol 90:1191–1197.  https://doi.org/10.1189/jlb.1110608 CrossRefGoogle Scholar
  78. 78.
    Schmid M, Zimara N, Wege AK, Ritter U (2014) Myeloid-derived suppressor cell functionality and interaction with Leishmania major parasites differ in C57BL/6 and BALB/c mice. Eur J Immunol 44:3295–3306.  https://doi.org/10.1002/eji.201344335 CrossRefGoogle Scholar
  79. 79.
    Singh A, Lelis F, Braig S et al (2016) Differential regulation of myeloid-derived suppressor cells by Candida species. Front Microbiol 7:1624.  https://doi.org/10.3389/fmicb.2016.01624 Google Scholar
  80. 80.
    Zhang C, Lei G-S, Shao S et al (2012) Accumulation of myeloid-derived suppressor cells in the lungs during Pneumocystis pneumonia. Infect Immun 80:3634–3641.  https://doi.org/10.1128/IAI.00668-12 CrossRefGoogle Scholar
  81. 81.
    Lei G-S, Zhang C, Shao S et al (2013) All-trans retinoic acid in combination with primaquine clears pneumocystis infection. PLoS One 8:e53479.  https://doi.org/10.1371/journal.pone.0053479 CrossRefGoogle Scholar
  82. 82.
    Lei G-S, Zhang C, Lee C-H (2015) Myeloid-derived suppressor cells impair alveolar macrophages through PD-1 receptor ligation during Pneumocystis pneumonia. Infect Immun 83:572–582.  https://doi.org/10.1128/IAI.02686-14 CrossRefGoogle Scholar
  83. 83.
    Sui Y, Frey B, Wang Y et al (2017) Paradoxical myeloid-derived suppressor cell reduction in the bone marrow of SIV chronically infected macaques. PLoS Pathog 13:e1006395.  https://doi.org/10.1371/journal.ppat.1006395 CrossRefGoogle Scholar
  84. 84.
    Keller C, Hoffmann R, Lang R et al (2006) Genetically determined susceptibility to tuberculosis in mice causally involves accelerated and enhanced recruitment of granulocytes. Infect Immun 74:4295–4309.  https://doi.org/10.1128/IAI.00057-06 CrossRefGoogle Scholar
  85. 85.
    Eruslanov EB, Lyadova IV, Kondratieva TK et al (2005) Neutrophil responses to Mycobacterium tuberculosis infection in genetically susceptible and resistant mice. Infect Immun 73:1744–1753.  https://doi.org/10.1128/IAI.73.3.1744-1753.2005 CrossRefGoogle Scholar
  86. 86.
    Tebartz C, Horst SA, Sparwasser T et al (2015) A major role for myeloid-derived suppressor cells and a minor role for regulatory T cells in immunosuppression during Staphylococcus aureus infection. J Immunol 194:1100–1111.  https://doi.org/10.4049/jimmunol.1400196 CrossRefGoogle Scholar
  87. 87.
    Mourik BC, Leenen PJM, de Knegt GJ et al (2017) Immunotherapy added to antibiotic treatment reduces relapse of disease in a mouse model of tuberculosis. Am J Respir Cell Mol Biol 56:233–241.  https://doi.org/10.1165/rcmb.2016-0185OC Google Scholar
  88. 88.
    Chandra D, Quispe-Tintaya W, Jahangir A et al (2014) STING ligand c-di-GMP improves cancer vaccination against metastatic breast cancer. Cancer Immunol Res 2:901–910.  https://doi.org/10.1158/2326-6066.CIR-13-0123 CrossRefGoogle Scholar
  89. 89.
    Liu F, Li X, Lu C et al (2016) Ceramide activates lysosomal cathepsin B and cathepsin D to attenuate autophagy and induces ER stress to suppress myeloid-derived suppressor cells. Oncotarget 7:83907–83925.  https://doi.org/10.18632/oncotarget.13438 Google Scholar
  90. 90.
    Tavazoie MF, Pollack I, Tanqueco R et al (2018) LXR/ApoE activation restricts innate immune suppression in cancer. Cell 172:825–840.e18.  https://doi.org/10.1016/j.cell.2017.12.026 CrossRefGoogle Scholar
  91. 91.
    Ahidjo BA, Bishai WR (2016) Phosphodiesterase inhibitors as adjunctive therapies for tuberculosis. EBioMedicine 4:7–8.  https://doi.org/10.1016/j.ebiom.2016.02.016 CrossRefGoogle Scholar
  92. 92.
    Obregón-Henao A, Henao-Tamayo M, Orme IM, Ordway DJ (2013) Gr1(int)CD11b+ myeloid-derived suppressor cells in Mycobacterium tuberculosis infection. PLoS One 8:e80669.  https://doi.org/10.1371/journal.pone.0080669 CrossRefGoogle Scholar
  93. 93.
    Vilaplana C, Marzo E, Tapia G et al (2013) Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis. J Infect Dis 208:199–202.  https://doi.org/10.1093/infdis/jit152 CrossRefGoogle Scholar
  94. 94.
    Zhang S, Wu K, Liu Y et al (2016) Finasteride Enhances the generation of human myeloid-derived suppressor cells by up-regulating the COX2/PGE2 pathway. PLoS One 11:e0156549.  https://doi.org/10.1371/journal.pone.0156549 CrossRefGoogle Scholar
  95. 95.
    Rieber N, Gille C, Köstlin N et al (2013) Neutrophilic myeloid-derived suppressor cells in cord blood modulate innate and adaptive immune responses. Clin Exp Immunol 174:45–52.  https://doi.org/10.1111/cei.12143 CrossRefGoogle Scholar
  96. 96.
    Flores RR, Clauson CL, Cho J et al (2017) Expansion of myeloid-derived suppressor cells with aging in the bone marrow of mice through a NF-κB-dependent mechanism. Aging Cell 16:480–487.  https://doi.org/10.1111/acel.12571 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Immunology, Friedrich-Loeffler-InstitutFederal Research Institute for Animal HealthGreifswaldGermany
  2. 2.Faculty of Mathematics and Natural SciencesUniversity of GreifswaldGreifswaldGermany
  3. 3.Department of ImmunologyMax Planck Institute for Infection BiologyBerlinGermany
  4. 4.Nuclear Receptor Group, Department of Cell Biology, Physiology and Immunology, School of BiologyUniversity of BarcelonaBarcelonaSpain
  5. 5.Institute of Biomedicine of the University of Barcelona (IBUB)BarcelonaSpain
  6. 6.Institut Pasteur, HIV Inflammation and Persistence UnitParisFrance
  7. 7.Institute of Virology, University Hospital EssenUniversity of Duisburg-EssenEssenGermany
  8. 8.Immunology of Viral Infections and Autoimmune Diseases (IMVA), IDMIT DepartmentCEA, Université Paris Sud 11, INSERM U1184, IBJFFontenay-aux-RosesFrance
  9. 9.University Children’s Hospital and Interdisciplinary Center for Infectious DiseasesUniversity of TübingenTübingenGermany
  10. 10.Department of DermatologyUniversity Hospital MünsterMünsterGermany
  11. 11.Viral Immunobiology, Institute of Experimental ImmunologyUniversity of ZürichZurichSwitzerland
  12. 12.i3S-Instituto de Investigação e Inovação em SaúdePortoPortugal
  13. 13.IBMC, Instituto de Biologia Molecular e CelularUniversidade do PortoPortoPortugal
  14. 14.Molecular and Translational Cardiology, Department of Cardiovascular MedicineUniversity Hospital MünsterMünsterGermany
  15. 15.Institute of Molecular Genetics of the Czech Academy of SciencesPragueCzech Republic
  16. 16.Instituto de Medicina Molecular, Faculdade de MedicinaUniversidade de LisboaLisbonPortugal
  17. 17.Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary SciencesUniversity of AntwerpAntwerpBelgium

Personalised recommendations