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Medical Microbiology and Immunology

, Volume 208, Issue 1, pp 39–48 | Cite as

β-Glucan induces autophagy in dendritic cells and influences T-cell differentiation

  • Jun Ding
  • Yongling Ning
  • Yu Bai
  • Ximing Xu
  • Xiao Sun
  • Chunjian QiEmail author
Original Investigation

Abstract

β-Glucan has been reported to activate dendritic cells (DCs), and activated DCs, subsequently, promote Th1 and cytotoxic T-lymphocyte priming and differentiation in vitro. However, the mechanism that regulates the immune response of β-glucan-induced DCs has not been thoroughly elucidated to date. Recent studies have drawn attention to a strong relationship between pathogen-associated molecular patterns (PAMP) recognition and autophagy for the activation of DC function. In this study, we observed that β-glucan induced the expression of a number of autophagy-related genes and the formation of autophagosomes in DCs. To further investigate whether β-glucan-induced DC activation and innate cytokine production are associated with autophagy, we utilized 3-MA to block autophagosome formation and accessed the maturation and function of DCs induced by β-glucan. We found that autophagy-deficient DCs showed downregulated expression of MHC-II and CD80, decreased TNF-α secretion, and reduced production of iNOS upon β-glucan stimulation. Further examination demonstrated that blockade of autophagy in β-glucan-induced DCs significantly attenuated IFN-γ production by co-cultured CD4 + T cells and inhibited the proliferation and differentiation of CD4 + T cells. Thus, these data indicate that autophagy in β-glucan-induced DCs is a crucial mechanism for the maturation of DCs, and it drives innate cytokine production, thereby facilitating adaptive immune responses.

Keywords

β-Glucan Dendritic cells Autophagy T-cell differentiation 

Notes

Acknowledgements

This work was supported by National Natural Science Foundation of China (81672799 to C.Q. and 31500731 to Y.N.) and the Changzhou Sci & Tech Program (CJ20160017 to J.D.).

Compliance with ethical standards

Conflict of interest

The author’s declare that they have no conflict of interest.

Supplementary material

430_2018_556_MOESM1_ESM.docx (567 kb)
Supplementary material 1 (DOCX 566 KB)

References

  1. 1.
    Di Luzio NR, Williams DL, McNamee RB, Edwards BF, Kitahama A (1979) Comparative tumor-inhibitory and anti-bacterial activity of soluble and particulate glucan. Int J Cancer 24(6):773–779CrossRefGoogle Scholar
  2. 2.
    Diller IC, Mankowski ZT, Fisher ME (1963) The effect of yeast polysaccharides on mouse tumors. Cancer Res 23:201–208Google Scholar
  3. 3.
    Hunter JT, Meltzer MS, Ribi E, Fidler IJ, Hanna MG Jr, Zbar B, Rapp HJ (1978) Glucan: attempts to demonstrate therapeutic activity against five syngeneic tumors in guinea pigs and mice. J Natl Cancer Inst 60(2):419–424CrossRefGoogle Scholar
  4. 4.
    Tsoni SV, Brown GD (2008) beta-Glucans and dectin-1. Ann N Y Acad Sci 1143:45–60.  https://doi.org/10.1196/annals.1443.019 CrossRefGoogle Scholar
  5. 5.
    Ensley HE, Tobias B, Pretus HA, McNamee RB, Jones EL, Browder IW, Williams DL (1994) NMR spectral analysis of a water-insoluble (1–>3)-beta-d-glucan isolated from Saccharomyces cerevisiae. Carbohydr Res 258:307–311CrossRefGoogle Scholar
  6. 6.
    Lipinski T, Fitieh A, St Pierre J, Ostergaard HL, Bundle DR, Touret N (2013) Enhanced immunogenicity of a tricomponent mannan tetanus toxoid conjugate vaccine targeted to dendritic cells via Dectin-1 by incorporating beta-glucan. J Immunol 190(8):4116–4128.  https://doi.org/10.4049/jimmunol.1202937 CrossRefGoogle Scholar
  7. 7.
    Qi C, Cai Y, Gunn L, Ding C, Li B, Kloecker G, Qian K, Vasilakos J, Saijo S, Iwakura Y, Yannelli JR, Yan J (2011) Differential pathways regulating innate and adaptive antitumor immune responses by particulate and soluble yeast-derived beta-glucans. Blood 117(25):6825–6836.  https://doi.org/10.1182/blood-2011-02-339812 CrossRefPubMedCentralGoogle Scholar
  8. 8.
    Li B, Cai Y, Qi C, Hansen R, Ding C, Mitchell TC, Yan J (2010) Orally administered particulate beta-glucan modulates tumor-capturing dendritic cells and improves antitumor T-cell responses in cancer. Clin Cancer Res 16(21):5153–5164.  https://doi.org/10.1158/1078-0432.CCR-10-0820 CrossRefPubMedCentralGoogle Scholar
  9. 9.
    Ning Y, Xu D, Zhang X, Bai Y, Ding J, Feng T, Wang S, Xu N, Qian K, Wang Y, Qi C (2016) Beta-Glucan restores tumor-educated dendritic cell maturation to enhance antitumor immune responses. Int J Cancer 138(11):2713–2723.  https://doi.org/10.1002/ijc.30002 CrossRefGoogle Scholar
  10. 10.
    Ding J, Feng T, Ning Y, Li W, Wu Q, Qian K, Wang Y, Qi C (2015) Beta-Glucan enhances cytotoxic T lymphocyte responses by activation of human monocyte-derived dendritic cells via the PI3K/AKT pathway. Hum Immunol 76(2–3):146–154.  https://doi.org/10.1016/j.humimm.2015.01.009 CrossRefGoogle Scholar
  11. 11.
    Li Y, Wang LX, Pang P, Twitty C, Fox BA, Aung S, Urba WJ, Hu HM (2009) Cross-presentation of tumor associated antigens through tumor-derived autophagosomes. Autophagy 5(4):576–577CrossRefPubMedCentralGoogle Scholar
  12. 12.
    Uhl M, Kepp O, Jusforgues-Saklani H, Vicencio JM, Kroemer G, Albert ML (2009) Autophagy within the antigen donor cell facilitates efficient antigen cross-priming of virus-specific CD8 + T cells. Cell Death Differ 16(7):991–1005.  https://doi.org/10.1038/cdd.2009.8 CrossRefGoogle Scholar
  13. 13.
    Zhou D, Li P, Lin Y, Lott JM, Hislop AD, Canaday DH, Brutkiewicz RR, Blum JS (2005) Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens. Immunity 22(5):571–581.  https://doi.org/10.1016/j.immuni.2005.03.009 CrossRefGoogle Scholar
  14. 14.
    Harris J, Master SS, De Haro SA, Delgado M, Roberts EA, Hope JC, Keane J, Deretic V (2009) Th1–Th2 polarisation and autophagy in the control of intracellular mycobacteria by macrophages. Vet Immunol Immunopathol 128(1–3):37–43.  https://doi.org/10.1016/j.vetimm.2008.10.293 CrossRefGoogle Scholar
  15. 15.
    Cooney R, Baker J, Brain O, Danis B, Pichulik T, Allan P, Ferguson DJ, Campbell BJ, Jewell D, Simmons A (2010) NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med 16(1):90–97.  https://doi.org/10.1038/nm.2069 CrossRefGoogle Scholar
  16. 16.
    Khan N, Vidyarthi A, Pahari S, Negi S, Aqdas M, Nadeem S, Agnihotri T, Agrewala JN (2016) Signaling through NOD-2 and TLR-4 Bolsters the T cell priming capability of dendritic cells by inducing autophagy. Sci Rep 6:19084.  https://doi.org/10.1038/srep19084 CrossRefPubMedCentralGoogle Scholar
  17. 17.
    Mintern JD, Macri C, Chin WJ, Panozza SE, Segura E, Patterson NL, Zeller P, Bourges D, Bedoui S, McMillan PJ, Idris A, Nowell CJ, Brown A, Radford KJ, Johnston AP, Villadangos JA (2015) Differential use of autophagy by primary dendritic cells specialized in cross-presentation. Autophagy 11(6):906–917.  https://doi.org/10.1080/15548627.2015.1045178 CrossRefPubMedCentralGoogle Scholar
  18. 18.
    Chiang HL, Terlecky SR, Plant CP, Dice JF (1989) A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science 246(4928):382–385CrossRefGoogle Scholar
  19. 19.
    Cuervo AM, Dice JF, Knecht E (1997) A population of rat liver lysosomes responsible for the selective uptake and degradation of cytosolic proteins. J Biol Chem 272(9):5606–5615CrossRefGoogle Scholar
  20. 20.
    Xie Z, Klionsky DJ (2007) Autophagosome formation: core machinery and adaptations. Nat Cell Biol 9(10):1102–1109.  https://doi.org/10.1038/ncb1007-1102 CrossRefGoogle Scholar
  21. 21.
    Deretic V, Saitoh T, Akira S (2013) Autophagy in infection, inflammation and immunity. Nat Rev Immunol 13(10):722–737.  https://doi.org/10.1038/nri3532 CrossRefPubMedCentralGoogle Scholar
  22. 22.
    Levine B, Deretic V (2007) Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol 7(10):767–777.  https://doi.org/10.1038/nri2161 CrossRefGoogle Scholar
  23. 23.
    Schmid D, Munz C (2007) Innate and adaptive immunity through autophagy. Immunity 27(1):11–21.  https://doi.org/10.1016/j.immuni.2007.07.004 CrossRefGoogle Scholar
  24. 24.
    Loi M, Gannage M, Munz C (2016) ATGs help MHC class II, but inhibit MHC class I antigen presentation. Autophagy 12(9):1681–1682.  https://doi.org/10.1080/15548627.2016.1203488 CrossRefPubMedCentralGoogle Scholar
  25. 25.
    Loi M, Muller A, Steinbach K, Niven J, Barreira da Silva R, Paul P, Ligeon LA, Caruso A, Albrecht RA, Becker AC, Annaheim N, Nowag H, Dengjel J, Garcia-Sastre A, Merkler D, Munz C, Gannage M (2016) Macroautophagy proteins control MHC class I levels on dendritic cells and shape anti-viral CD8(+) T cell responses. Cell Rep 15(5):1076–1087.  https://doi.org/10.1016/j.celrep.2016.04.002 CrossRefGoogle Scholar
  26. 26.
    Munz C (2010) Antigen processing via autophagy—not only for MHC class II presentation anymore? Curr Opin Immunol 22(1):89–93.  https://doi.org/10.1016/j.coi.2010.01.016 CrossRefPubMedCentralGoogle Scholar
  27. 27.
    Munz C (2016) Autophagy beyond intracellular MHC class II antigen presentation. Trends Immunol 37(11):755–763.  https://doi.org/10.1016/j.it.2016.08.017 CrossRefGoogle Scholar
  28. 28.
    Tam JM, Mansour MK, Khan NS, Seward M, Puranam S, Tanne A, Sokolovska A, Becker CE, Acharya M, Baird MA, Choi AM, Davidson MW, Segal BH, Lacy-Hulbert A, Stuart LM, Xavier RJ, Vyas JM (2014) Dectin-1-dependent LC3 recruitment to phagosomes enhances fungicidal activity in macrophages. J Infect Dis 210(11):1844–1854.  https://doi.org/10.1093/infdis/jiu290 CrossRefPubMedCentralGoogle Scholar
  29. 29.
    Lamprinaki D, Beasy G, Zhekova A, Wittmann A, James S, Dicks J, Iwakura Y, Saijo S, Wang X, Chow CW, Roberts I, Korcsmaros T, Mayer U, Wileman T, Kawasaki N (2017) LC3-associated phagocytosis is required for dendritic cell inflammatory cytokine response to gut commensal yeast Saccharomyces cerevisiae. Front Immunol 8:1397.  https://doi.org/10.3389/fimmu.2017.01397 CrossRefPubMedCentralGoogle Scholar
  30. 30.
    Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811.  https://doi.org/10.1146/annurev.immunol.18.1.767 CrossRefGoogle Scholar
  31. 31.
    Rutella S, Danese S, Leone G (2006) Tolerogenic dendritic cells: cytokine modulation comes of age. Blood 108(5):1435–1440.  https://doi.org/10.1182/blood-2006-03-00640 CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Medical Research Center, The Affiliated Changzhou No. 2 People’s HospitalNanjing Medical UniversityChangzhouChina
  2. 2.Oncology Institute, The Affiliated Changzhou No. 2 People’s HospitalNanjing Medical UniversityChangzhouChina
  3. 3.Institute of Bioinformatics and Medical Engineering, School of Electrical and Information EngineeringJiangsu University of TechnologyChangzhouChina

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