Original Article

The Opposite Effects of DNA and Protein Components of Listeria Monocytogenes and Toxoplasma gondii on Immunologic Characteristics of Dendritic Cells


The innate immune system utilizes pattern recognition receptors (PRRs) to recognize microbes. Pathogens contain various molecules with diverse effects on immune response. In this study, we evaluated the effect of DNA and protein components derived from two intracellular microorganisms including Listeria monocytogenes (L.monocytogenes) and Toxoplasma gondii (T. gondii) on dendritic cells (DCs) activation and ensuing adaptive immune responses.DNA and protein components of L. monocytogenes and T. gondii were prepared using relevant kits. DNA and protein components of these two pathogens were added to immature DCs (iDCs). Subsequently, co-stimulatory expression and cytokine production by DCs were measured. Finally, we evaluated the stimulatory capacity of mature DCs (mDCs) in DC-T cells co-culture.The results showed that protein matured-DCs produced higher level of IL (Interleukin)-12p70. There was also a significant increase in Interferon-Gamma (IFN-γ) production and proliferative capacity in T cells co- cultured with protein matured-DCs. On the other hand, DNA matured-DCs produced significantly higher amounts of Transforming growth factor-beta (TGF-β).Collectively, these results imply a regulatory nature for DNA and potent stimulatory character for protein components of these two intracellular microorganisms.

1. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature 2007;449(7164):819-26.

2. Raupach B, Kaufmann SH. Immune responses to intracellular bacteria. Curr Opin Immunol 2001;13(4):417-28.

3. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006; 124(4):783-801.

4. Crozat K, Vivier E, Dalod M. Crosstalk between components of the innate immune system: promoting anti-microbial defenses and avoiding immunopathologies. Immunol Rev 2009; 227(1):129-49.

5. Akira S, Takeda K, Kaisho T. Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2001; 2(8):675-80.

6. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010; 11(5):373-84.

7. Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. Int Rev Immunol 2011; 30(1):16-34.

8. Sansonetti PJ, Di Santo JP. Debugging how bacteria manipulate the immune response. Immunity 2007;26(2):149-61.

9. Kapsenberg ML. Dendritic-cell control of pathogen- driven T-cell polarization. Nat Rev Immunol 2003;3(12):984-93.

10. Belkaid Y. Regulatory T cells and infection: a dangerous necessity. Nat Rev Immunol 2007; 7(11):875-88.

11. Kushwah R, Hu J. Complexity of dendritic cell subsets and their function in the host immune system. Immunology 2011; 133(4):409-19.

12. Satpathy AT, Wu X, Albring JC, Murphy KM.Re(de)fining the dendritic cell lineage. Nat Immunol 2012; 13(12):1145-54.

13. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998; 392(6673):245-52.

14. Reis e Sousa C, Sher A, Kaye P. The role of dendritic cells in the induction and regulation of immunity to microbial infection. Curr Opin Immunol 1999; 11(4):392-9.

15. Jonuleit H, Schmitt E, Schuler G, Knop J, Enk AH.Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J Exp Med 2000; 192(9):1213-22.

16. Norbury CC. Drinking a lot is good for dendritic cells.Immunology 2006; 117(4):443-51.

17. 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(6):863-9.

18. Pamer EG. Immune responses to Listeria monocytogenes.Nat Rev Immunol 2004; 4(10):812-23.

19. Filisetti D, Candolfi E. Immune response to Toxoplasma gondii. Ann Ist Super Sanita 2004; 40(1):71-80.

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(10):1393-8.

21. 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(1):36-44.

22. Khan IA, Matsuura T, Kasper LH. IL-10 mediates immunosuppression following primary infection with Toxoplasma gondii in mice. Parasite Immunol 1995;17(4):185-95.

23. Frei K, Nadal D, Pfister HW, Fontana A. Listeria meningitis: identification of a cerebrospinal fluid inhibitor of macrophage listericidal function as interleukin 10. J Exp Med 1993; 178(4):1255-61.

24. Dubey JP, Shen SK, Kwok OC, Frenkel JK. Infection and immunity with the RH strain of Toxoplasma gondii in rats and mice. J Parasitol 1999; 85(4):657-62.

25. Inaba K, Swiggard WJ, Steinman RM, Romani N, Schuler G. Isolation of dendritic cells. Curr Protoc Immunol 2001; Chapter 3:Unit 3 7.

26. Sher A, Pearce E, Kaye P. Shaping the immune response to parasites: role of dendritic cells. Curr Opin Immunol 2003; 15(4):421-9.

27. de Jong EC, Vieira PL, Kalinski P, Schuitemaker JH, Tanaka Y, Wierenga EA, et al. Microbial compounds selectively induce Th1 cell-promoting or Th2 cell- promoting dendritic cells in vitro with diverse th cell- polarizing signals. J Immunol 2002; 168(4):1704-9.

28. 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):1-10.

29. Ouaissi A, Guilvard E, Delneste Y, Caron G, Magistrelli G, Herbault N, et al. The Trypanosoma cruzi Tc52-released protein induces human dendritic cell maturation, signals via Toll-like receptor 2, and confers protection against lethal infection. J Immunol 2002; 168(12):6366-74.

30. Hertz CJ, Kiertscher SM, Godowski PJ, Bouis DA,Norgard MV, Roth MD, et al. Microbial lipopeptides stimulate dendritic cell maturation via Toll-like receptor 2. J Immunol 2001; 166(4):2444-50.

31. Wood LM, Pan ZK, Shahabi V, Paterson Y. Listeria- derived ActA is an effective adjuvant for primary and metastatic tumor immunotherapy. Cancer Immunol Immunother 2010; 59(7):1049-58.

32. Yarovinsky F, Zhang D, Andersen JF, Bannenberg GL,Serhan CN, Hayden MS, et al. TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science 2005; 308(5728):1626-9.

33. Bauer M, Redecke V, Ellwart JW, Scherer B, Kremer JP, Wagner H, et al. Bacterial CpG-DNA triggers activation and maturation of human CD11c-, CD123+ dendritic cells. J Immunol 2001; 166(8):5000-7.

34. Fallarino F, Puccetti P. Toll-like receptor 9-mediated induction of the immunosuppressive pathway of tryptophan catabolism. Eur J Immunol 2006; 36(1):8-11.

35. Wingender G, Garbi N, Schumak B, Jungerkes F, Endl E, von Bubnoff D, et al. Systemic application of CpG-rich DNA suppresses adaptive T cell immunity via induction of IDO. Eur J Immunol 2006; 36(1):12-20.

36. Vollmer J, Weeratna RD, Jurk M, Samulowitz U,McCluskie MJ, Payette P, et al. Oligodeoxynucleotides lacking CpG dinucleotides mediate Toll-like receptor 9 dependent T helper type 2 biased immune stimulation. Immunology 2004; 113(2):212-23.

37. 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(9):5601-5.

38. 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(2):360-4.

39. Trinchieri G, Sher A. Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol 2007; 7(3):179-90.

IssueVol 14, No 3 (2015) QRcode
SectionOriginal Article(s)
Dendritic cells Immunity Listeria monocytogenes Toxoplasma gondii

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Mirzaei R, Arab S, Motamedi M, Amari A, Hadjati J. 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):313-320.