Listeria Monocytogenes Protein Fraction Induces Dendritic Cells Maturation and T helper 1 Immune Responses
Abstract
Fully mature dendritic cells (DCs) play pivotal role in inducing immune responses and converting naïve T lymphocytes into functional Th1 cells. We aimed to evaluate Listeria Monocytogenes-derived protein fractions to induce DC maturation and stimulating T helper (Th)1 immune responses.
In the present study, we fractionated Listeria Monocytogenes-derived proteins by adding of ammonium sulfate in a stepwise manner. DCs were also generated from C57BL/6 mice bone marrow precursor cells. Then, the effects of protein fractions on bone marrow derived DC (BMDC) maturation were evaluated. In addition, we assessed the capacity of activated DCs to induce cytokine production and proliferation of lymphocytes.
Listeria-derived protein fractions induced fully mature DCs expressing high costimulatory molecules such as CD80, CD86 and CD40. DCs that were activated by selected F3 fraction had low capacity to uptake exogenous antigens while secreted high levels of Interleukine (IL)-12. Moreover, lymphocytes cultured with activated BMDCs produced high amounts of IFN-γ and showed higher proliferation than control. Listeria derived protein fractions differently influenced DC maturation.
In conclusion, Listeria protein activated-BMDCs can be used as a cell based vaccine to induce anti-tumor immune responses.
1. Iwasaki A, Medzhitov R. Regulation of adaptive immunity by the innate immune system. Science 2010;327(5963):291-5.
2. Nakano H, Lin KL, Yanagita M, Charbonneau C, Cook DN, Kakiuchi T, et al. Blood-derived inflammatory dendritic cells in lymph nodes stimulate acute T helper type 1 immune responses. Nat Immunol 2009; 10(4):394-402.
3. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, et al. Immunobiology of dendritic cells. Annu Rev Immunol 2000; 18(1):767-811.
4. Song S, Wang Y, Wang J, Lian W, Liu S, Zhang Z, et al.Tumour-derived IL-10 within tumour microenvironment represses the antitumour immunity of Socs1-silenced and sustained antigen expressing DCs. Eur J Cancer 2012;48(14):2252-9.
5. Roy RM, Klein BS. Dendritic cells in antifungal immunity and vaccine design. Cell Host Microbe 2012;11(5):436-46.
6. Manicassamy S, Pulendran B. Dendritic cell control of tolerogenic responses. Immunol Rev 2011; 241(1):206-27.
7. Swiatczak B, Rescigno M, editors. How the interplay between antigen presenting cells and microbiota tunes host immune responses in the gut. Semin Immunol 2011;24(1):43-9.
8. Pantel A, Cheong C, Dandamudi D, Shrestha E, Mehandru S, Brane L, et al. A new synthetic TLR4 agonist, GLA, allows dendritic cells targeted with antigen to elicit Th1 T‐cell immunity in vivo. Eur J Immunol 2012; 42(1):101-9.
9. Vremec D, O'Keeffe M, Wilson A, Ferrero I, Koch U, Radtke F, et al. Factors determining the spontaneous activation of splenic dendritic cells in culture. Innate immun 2011; 17(3):338-52.
10. Vallabhapurapu S, Karin M. Regulation and function of NF-κB transcription factors in the immune system. Annu Rev Immunol 2009; 27:693-733.
11. Hedayat M, Takeda K, Rezaei N. Prophylactic and therapeutic implications of toll‐like receptor ligands. Medicinal research reviews. 2012.
12. Palucka K, Banchereau J. How dendritic cells and microbes interact to elicit or subvert protective immune responses. Curr Opin Immunol 2002; 14(4):420-31.
13. de Jong EC, Vieira PL, Kalinski P, Schuitemaker JHN, 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.
14. Hitzler I, Oertli M, Becher B, Agger EM, Müller A.Dendritic Cells Prevent Rather Than Promote Immunity Conferred by a Helicobacter Vaccine Using a Mycobacterial Adjuvant. Gastroenterology 2011;141(1):186-96.
15. Carreño LJ, Riedel CA, Kalergis AM. Induction of Tolerogenic Dendritic Cells by NF-kB Blockade and Fcg Receptor Modulation. Methods Mol Biol 2011; 677:339-53.
16. Medzhitov R, Janeway C. Innate immunity: Minireview the virtues of a nonclonal system of recognition. Cell 1997; 91(3):295-8.
17. Hemmi H, Akira S. A novel Toll-like receptor that recognizes bacterial DNA. Microbial DNA and Host Immunity 2002:39-47.
18. Pamer EG. Immune responses to Listeria monocytogenes.Nat Rev Immunol 2004; 4(10):812-23.
19. Vázquez-Boland JA, Kuhn M, Berche P, Chakraborty T, Domı$nguez-Bernal G, Goebel W, et al. Listeria pathogenesis and molecular virulence determinants. Clin Microbiol Rev 2001; 14(3):584-640.
20. Fedele G, Stefanelli P, Spensieri F, Fazio C, Mastrantonio P, Ausiello CM. Bordetella pertussis-infected human monocyte-derived dendritic cells undergo maturation and induce Th1 polarization and interleukin-23 expression. Infect Immun 2005; 73(3):1590-7.
21. Brzoza KL, Rockel AB, Hiltbold EM. Cytoplasmic entry of Listeria monocytogenes enhances dendritic cell maturation and T cell differentiation and function. J Immunol 2004; 173(4):2641-51.
22. Ainscough JS, Frank Gerberick G, Dearman RJ, Kimber I. Danger, intracellular signaling, and the orchestration of dendritic cell function in skin sensitization. J Immunotoxicol 2012.
23. Warren SE, Mao DP, Rodriguez AE, Miao EA, Aderem A. Multiple Nod-like receptors activate caspase 1 during Listeria monocytogenes infection. J Immunol 2008;180(11):7558-64.
24. Hamon M, Bierne H, Cossart P. Listeria monocytogenes:a multifaceted model. Nat Rev Microbiol 2006; 4(6):423-34.
25. Portnoy DA, Auerbuch V, Glomski IJ. The cell biology of Listeria monocytogenes infection the intersection of bacterial pathogenesis and cell-mediated immunity. J Cell Biol 2002; 158(3):409-14.
26. Williams MA, Schmidt RL, Lenz LL. Early events regulating immunity and pathogenesis during Listeria monocytogenes infection. Trends Immunol 2012;33(10):488-95.
27. Olino K, Wada S, Edil BH, Pan X, Meckel K, Weber W, et al. Tumor-associated antigen expressing Listeria monocytogenes induces effective primary and memory T- cell responses against hepatic colorectal cancer metastases. Ann Surg Oncol 2011; 19 Suppl 3:S597-607.
28. Chen Y, Yang D, Li S, Gao Y, Jiang R, Deng L, et al.Development of a Listeria monocytogenes-based vaccine against hepatocellular carcinoma. Oncogene 2011;31(17):2140-52.
29. Guirnalda P, Paterson Y. Vaccination with immunotherapeutic Listeria monocytogenes induces IL-17+ γδ T cells in a murine model for HPV associated cancer. Oncoimmunology 2012; 1(6):822-8.
30. Olive C. Pattern recognition receptors: sentinels in innate immunity and targets of new vaccine adjuvants. Expert Rev Vaccines 2012; 11(2):237-56.
31. Kim S, Bauernfeind F, Ablasser A, Hartmann G,Fitzgerald KA, Latz E, et al. Listeria monocytogenes is sensed by the NLRP3 and AIM2 inflammasome. Eur J Immunol 2010; 40(6):1545-51.
32. Miller MA, Skeen MJ, Ziegler H. Protective Immunity to Listeria monocytogenes Elicited by Immunization with Heat‐Killed Listeria and IL‐12. Ann N Y Acad Sci 2006;797(1):207-27.
33. Yeung VP, Gieni RS, Umetsu DT, DeKruyff RH. Heat- killed Listeria monocytogenes as an adjuvant converts established murine Th2-dominated immune responses into Th1-dominated responses. J Immunol 1998;161(8):4146-52.
34. Tacken PJ, de Vries IJM, Torensma R, Figdor CG.Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. Nat Rev Immunol 2007; 7(10):790-802.
35. Tacken PJ, Figdor CG. Targeted antigen delivery and activation of dendritic cells in vivo: steps towards cost effective vaccines. Semin Immunol 2011; 23(1):12-20.
36. 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.
37. Inaba K, Inaba M, Naito M, Steinman R. Dendritic cell progenitors phagocytose particulates, including bacillus Calmette-Guerin organisms, and sensitize mice to mycobacterial antigens in vivo. J Exp Med 1993;178(2):479-88.
38. Arce F, Kochan G, Breckpot K, Stephenson H, Escors D.Selective activation of intracellular signalling pathways in dendritic cells for cancer immunotherapy. Anticancer Agents Med Chem 2012;12(1):29-39.
39. Kadowaki N. Dendritic cells: a conductor of T cell differentiation. Allergol Int 2007; 56(3):193-9.
40. Morton CO, Varga JJ, Hornbach A, Mezger M, Sennefelder H, Kneitz S, et al. The temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro. PloS one 2011; 6(1):e16016.
41. Christensen HR, Frøkiær H, Pestka JJ. Lactobacilli differentially modulate expression of cytokines and maturation surface markers in murine dendritic cells. J Immunol 2002; 168(1):171-8.
42. Richards J, Le Naour F, Hanash S, Beretta L. Integrated genomic and proteomic analysis of signaling pathways in dendritic cell differentiation and maturation. Ann N Y Acad Sci 2002; 975(1):91-100.
43. Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat immunol 2004;5(10):987-95.
44. Lutz MB, Schuler G. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol 2002; 23(9):445-9.
45. Manfred B, Lutz MB. Therapeutic potential of semi- mature dendritic cells for tolerance induction. Front Immunol 2012; 3:123.
46. Round JL, O'Connell RM, Mazmanian SK. Coordination of tolerogenic immune responses by the commensal microbiota. J Autoimmun 2010; 34(3):J220-J5.
47. Huang B, Zhao J, Shen S, Li H, He KL, Shen GX, et al.Listeria monocytogenes promotes tumor growth via tumor cell toll-like receptor 2 signaling. Cancer Res 2007;67(9):4346-52.
48. Hathcock KS, Laszlo G, Pucillo C, Linsley P, Hodes RJ.Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function. J Exp Med 1994;180(2):631-40.
49. Maruo S, Toyo-oka K, Oh-hora M, Tai XG, Iwata H, Takenaka H, et al. IL-12 produced by antigen-presenting cells induces IL-2-independent proliferation of T helper cell clones. J Immunol 1996; 156(5):1748-55.
50. Scharton TM, Scott P. Natural killer cells are a source of interferon gamma that drives differentiation of CD4+ T cell subsets and induces early resistance to Leishmania major in mice. J Exp Med 1993; 178(2):567-77.
51. Mack EA, Kallal LE, Demers DA, Biron CA. Type 1 interferon induction of natural killer cell gamma interferon production for defense during lymphocytic choriomeningitis virus infection. MBio 2011;2(4).
52. Szabo SJ, Sullivan BM, Stemmann C, Satoskar AR, Sleckman BP, Glimcher LH. Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science 2002; 295(5553):338-42.
53. Chapoval AI, Ni J, Lau JS, Wilcox RA, Flies DB, Liu D, et al. B7-H3: a costimulatory molecule for T cell activation and IFN-γ production. Nat Immunol 2001;2(3):269-74.
54. Steinman RM. Decisions about dendritic cells: past, present, and future. Annu Rev Immunol 2012; 30:1-22.
55. Vega-Ramos J, Villadangos JA. Consequences of direct and indirect activation of dendritic cells on antigen presentation: Functional implications and clinical considerations. Mol Immunol 2013; 55(2):175-8.
56. Cella M, Engering A, Pinet V, Pieters J, Lanzavecchia A.Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells. Nature 1997;388(6644):782-7.
57. Pierre P, Turley SJ, Gatti E, Hull M, Meltzer J, Mirza A, et al. Developmental regulation of MHC class II transport in mouse dendritic cells. Nature 1997; 388(6644):787-91.
58. Turley SJ, Inaba K, Garrett WS, Ebersold M,Unternaehrer J, Steinman RM, et al. Transport of peptide- MHC class II complexes in developing dendritic cells. Science 2000; 288(5465):522-7.
59. Sharma SD, Verhoef J, Remington JS. Enhancement of human natural killer cell activity by subcellular components of Toxoplasma gondii. Cell Immunol 1984;86(2):317-26.
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| Issue | Vol 13, No 1 (2014) | |
| Section | Articles | |
| Keywords | ||
| Dendritic cells Interferon gamma Interleukin-12 Listeria Monocytogenes | ||
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