Skip to main content

Advertisement

SpringerLink
Log in

Identification of proteins derived from Listeria monocytogenes inducing human dendritic cell maturation

  • Original Article
  • Published:
Tumor Biology

Abstract

Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that can promote antitumor immunity when pulsed with tumor antigens and then matured by stimulatory agents. Despite apparent progress in DC-based cancer immunotherapy, some discrepancies were reported in generating potent DCs. Listeria monocytogenes as an intracellular microorganism is able to effectively activate DCs through engaging pattern-recognition receptors (PRRs). This study aimed to find the most potent components derived from L. monocytogenes inducing DC maturation. The preliminary results demonstrated that the ability of protein components is higher than DNA components to promote DC maturation and activation. Protein lysate fractionation demonstrated that fraction 2 HIC (obtained by hydrophobic interaction chromatography) was able to efficiently mature DCs. F2HIC-matured DCs are able to induce allogeneic CD8+ T cells proliferation better than LPS-matured DCs and induce IFN-γ producing CD8+ T cells. Mass spectrometry results showed that F2HIC contains 109 proteins. Based on the bioinformatics analysis for these 109 proteins, elongation factor Tu (EF-Tu) could be considered as a PRR ligand for stimulating DC maturation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245–52.

    Article  CAS  PubMed  Google Scholar 

  2. Figdor CG, de Vries IJ, Lesterhuis WJ, Melief CJ. Dendritic cell immunotherapy: mapping the way. Nat Med. 2004;10:475–80.

    Article  CAS  PubMed  Google Scholar 

  3. Steinman RM, Banchereau J. Taking dendritic cells into medicine. Nature. 2007;449:419–26.

    Article  CAS  PubMed  Google Scholar 

  4. Schuler G, Schuler-Thurner B, Steinman RM. The use of dendritic cells in cancer immunotherapy. Curr Opin Immunol. 2003;15:138–47.

    Article  CAS  PubMed  Google Scholar 

  5. Lutz MB, Schuler G. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol. 2002;23:445–9.

    Article  CAS  PubMed  Google Scholar 

  6. Hilkens CM, Isaacs JD, Thomson AW. Development of dendritic cell-based immunotherapy for autoimmunity. Int Rev Immunol. 2010;29:156–83.

    Article  CAS  PubMed  Google Scholar 

  7. Rutella S, Danese S, Leone G. Tolerogenic dendritic cells: cytokine modulation comes of age. Blood. 2006;108:1435–40.

    Article  CAS  PubMed  Google Scholar 

  8. Langenkamp A, Messi M, Lanzavecchia A, Sallusto F. Kinetics of dendritic cell activation: impact on priming of th1, th2 and nonpolarized t cells. Nat Immunol. 2000;1:311–6.

    Article  CAS  PubMed  Google Scholar 

  9. Kapsenberg ML. Dendritic-cell control of pathogen-driven t-cell polarization. Nat Rev Immunol. 2003;3:984–93.

    Article  CAS  PubMed  Google Scholar 

  10. Reis e Sousa C. Dendritic cells as sensors of infection. Immunity. 2001;14:495–8.

    Article  CAS  PubMed  Google Scholar 

  11. Pamer EG. Immune responses to listeria monocytogenes. Nat Rev Immunol. 2004;4:812–23.

    Article  CAS  PubMed  Google Scholar 

  12. Khamisabadi M, Arab S, Motamedi M, Khansari N, Moazzeni SM, Gheflati Z, et al. Listeria monocytogenes activated dendritic cell based vaccine for prevention of experimental tumor in mice. Iran J Immunol. 2008;5:36–44.

    CAS  PubMed  Google Scholar 

  13. Saei A, Boghozian R, Mirzaei R, Jamali A, Vaziri B, Hadjati J. Listeria monocytogenes protein fraction induces dendritic cells maturation and t helper 1 immune responses. Iran J Allergy Asthma Immunol. 2014;13:1–10.

    CAS  PubMed  Google Scholar 

  14. Del Rio L, Butcher BA, Bennouna S, Hieny S, Sher A, Denkers EY. Toxoplasma gondii triggers myeloid differentiation factor 88-dependent il-12 and chemokine ligand 2 (monocyte chemoattractant protein 1) responses using distinct parasite molecules and host receptors. J Immunol. 2004;172:6954–60.

    Article  PubMed  Google Scholar 

  15. Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med. 1994;179:1109–18.

    Article  CAS  PubMed  Google Scholar 

  16. Nourizadeh M, Masoumi F, Memarian A, Alimoghaddam K, Moazzeni SM, Yaghmaie M, et al. In vitro induction of potent tumor-specific cytotoxic t lymphocytes using tlr agonist-activated aml-dc. Target Oncol. 2014;9:225–37.

    Article  PubMed  Google Scholar 

  17. Park MH, Yang DH, Kim MH, Jang JH, Jang YY, Lee YK, et al. Alpha-type 1 polarized dendritic cells loaded with apoptotic allogeneic breast cancer cells can induce potent cytotoxic t lymphocytes against breast cancer. Cancer Res Treat. 2011;43:56–66.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Keyvanshokooh S, Vaziri B, Gharaei A, Mahboudi F, Esmaili-Sari A, Shahriari-Moghadam M. Proteome modifications of juvenile beluga (huso huso) brain as an effect of dietary methylmercury. Comp Biochem Physiol Part D Genomics Proteomics. 2009;4:243–8.

    Article  PubMed  Google Scholar 

  19. Reza Mirzaei SA, Masoumeh Motamedi Motamedi, Afshin Amari, Jamshid Hadjati. The opposite effects of DNA and protein components of listeria monocytogenes and toxoplasma gondii on immunologic characteristics of dendritic cells. Iran J Allergy Asthma Immunol 2015;14(3):313–20.

  20. Motamedi M, Arab S, Moazzeni SM, Khamis Abadi M, Hadjati J. Improvement of a dendritic cell-based therapeutic cancer vaccine with components of toxoplasma gondii. Clin Vaccine Immunol. 2009;16:1393–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Pourgholaminejad A, Jamali A, Samadi-Foroushani M, Amari A, Mirzaei R, Ansaripour B, et al. Reduced efficacy of multiple doses of cpg-matured dendritic cell tumor vaccine in an experimental model. Cell Immunol. 2011;271:360–4.

    Article  CAS  PubMed  Google Scholar 

  22. Mellor AL, Baban B, Chandler PR, Manlapat A, Kahler DJ, Munn DH. Cutting edge: Cpg oligonucleotides induce splenic cd19+ dendritic cells to acquire potent indoleamine 2,3-dioxygenase-dependent t cell regulatory functions via ifn type 1 signaling. J Immunol. 2005;175:5601–5.

    Article  CAS  PubMed  Google Scholar 

  23. Moseman EA, Liang X, Dawson AJ, Panoskaltsis-Mortari A, Krieg AM, Liu YJ, et al. Human plasmacytoid dendritic cells activated by cpg oligodeoxynucleotides induce the generation of cd4+cd25+ regulatory t cells. J Immunol. 2004;173:4433–42.

    Article  CAS  PubMed  Google Scholar 

  24. Hoene V, Peiser M, Wanner R. Human monocyte-derived dendritic cells express tlr9 and react directly to the cpg-a oligonucleotide d19. J Leukoc Biol. 2006;80:1328–36.

    Article  CAS  PubMed  Google Scholar 

  25. Hartmann G, Weiner GJ, Krieg AM. Cpg DNA: a potent signal for growth, activation, and maturation of human dendritic cells. Proc Natl Acad Sci U S A. 1999;96:9305–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kadowaki N, Ho S, Antonenko S, Malefyt RW, Kastelein RA, Bazan F, et al. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med. 2001;194:863–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Re F, Strominger JL. Toll-like receptor 2 (tlr2) and tlr4 differentially activate human dendritic cells. J Biol Chem. 2001;276:37692–9.

    Article  CAS  PubMed  Google Scholar 

  28. Krab IM, Parmeggiani A. Ef-tu, a gtpase odyssey. Biochim Biophys Acta. 1998;1443:1–22.

    Article  CAS  PubMed  Google Scholar 

  29. Archambaud C, Gouin E, Pizarro-Cerda J, Cossart P, Dussurget O. Translation elongation factor ef-tu is a target for stp, a serine-threonine phosphatase involved in virulence of listeria monocytogenes. Mol Microbiol. 2005;56:383–96.

    Article  CAS  PubMed  Google Scholar 

  30. Liu H, Cheng Z, Song W, Wu W, Zhou Z. Immunoproteomic to analysis the pathogenicity factors in leukopenia caused by klebsiella pneumonia bacteremia. PLoS One. 2014;9:e110011.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Bunk S, Susnea I, Rupp J, Summersgill JT, Maass M, Stegmann W, et al. Immunoproteomic identification and serological responses to novel chlamydia pneumoniae antigens that are associated with persistent c. Pneumoniae infections. J Immunol. 2008;180:5490–8.

    Article  CAS  PubMed  Google Scholar 

  32. Gupta MK, Subramanian V, Yadav JS. Immunoproteomic identification of secretory and subcellular protein antigens and functional evaluation of the secretome fraction of mycobacterium immunogenum, a newly recognized species of the mycobacterium chelonae-mycobacterium abscessus group. J Proteome Res. 2009;8:2319–30.

    Article  CAS  PubMed  Google Scholar 

  33. Harding SV, Sarkar-Tyson M, Smither SJ, Atkins TP, Oyston PC, Brown KA, et al. The identification of surface proteins of burkholderia pseudomallei. Vaccine. 2007;25:2664–72.

    Article  CAS  PubMed  Google Scholar 

  34. Nieves W, Heang J, Asakrah S, Honer zu Bentrup K, Roy CJ, Morici LA. Immunospecific responses to bacterial elongation factor tu during burkholderia infection and immunization. PLoS One. 2010;5, e14361.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Sharma J, Mishra BB, Li Q, Teale JM. Tlr4-dependent activation of inflammatory cytokine response in macrophages by francisella elongation factor tu. Cell Immunol. 2011;269:69–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lopez JE, Beare PA, Heinzen RA, Norimine J, Lahmers KK, Palmer GH, et al. High-throughput identification of t-lymphocyte antigens from anaplasma marginale expressed using in vitro transcription and translation. J Immunol Methods. 2008;332:129–41.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Immunology Department, School of Medicine, Tehran University of Medical Sciences, Poursina Avenue, Tehran, Iran

    Reza Mirzaei, Azad Saei, Farshid Noorbakhsh & Jamshid Hadjati

  2. Protein Chemistry Unit, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

    Fatemeh Torkashvand, Bahareh Azarian & Behrouz Vaziri

  3. Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria

    Ahmad Jalili

Authors
  1. Reza Mirzaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Azad Saei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fatemeh Torkashvand
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bahareh Azarian
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ahmad Jalili
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Farshid Noorbakhsh
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Behrouz Vaziri
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jamshid Hadjati
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jamshid Hadjati.

Ethics declarations

Conflicts of interest

None

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mirzaei, R., Saei, A., Torkashvand, F. et al. Identification of proteins derived from Listeria monocytogenes inducing human dendritic cell maturation. Tumor Biol. 37, 10893–10907 (2016). https://doi.org/10.1007/s13277-016-4933-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-016-4933-1

Keywords

Search

Navigation