Biopolym. Cell. 2012; 28(1):50-55.
Structure and Function of Biopolymers
Synergistic effect of microbe-associated molecules on human monocyte-derived dendritic cell maturation in vitro
1Skivka L. M., 1Shvets Yu. V., 2Khranovska N. M., 3Fedorchuk O. G., 1Pozur V. V., 1Senchilo N. V.
  1. Educational and Scientific Center "Institute of Biology",
    Taras Shevchenko National University of Kyiv
    64/13, Volodymyrska Str., Kyiv, Ukraine, 01601
  2. National Cancer Institute
    33/43, Lomonosova Str., Kyiv, Ukraine, 03022
  3. R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine
    45, Vasilkivska Str., Kyiv, Ukraine, 01022


Microbe-associated molecules (MAM) are known to exert stimulating effect on the dendritic cell (DC) maturation. The aim of this investigation was a comparative study of the effect of different MAMs, used separately and in combination, on human monocyte-derived DC maturation in vitro. Methods. The studied MAMs were represented by lipopolysaccharide (LPS) from Escherichia coli and different biopolymers from Staphylococcus aureus Wood 46. DC phenotype was analyzed by flow cytometry. Functional maturity of DC was assessed in the mixed leukocyte reaction. Results. The use of MAMs in combination has been shown to be more efficient for phenotypic and functional maturation of monocyte-derived DCs than utilizing different MAMs separately. The most potent stimulatory effect has been observed for the combination of LPS with peptidoglycan (PepG) or teichoic acid with PepG. Conclusions. Combined use of different MAMs, especially those that activate different signaling pathways (LPS-PepG and teichoic acid-PepG), results in synergistic stimulation of monocyte-derived DC maturation.
Keywords: dendritic cells, lipopolysaccharide, teichoic acid, peptidoglycan


[1] Liu K., Nussenzweig M. C. Origin and development of dendritic cells. Immunol. Rev 2010 234, N 1:45–54.
[2] Palucka A. K., Ueno H., Fay J., Banchereau J. Dendritic cells: a critical player in cancer therapy?. J. Immunother 2008 31, N 9:793–805.
[3] Janikashvili N., Larmonier N., Katsanis E. Personalized dendritic cell-based tumor immunotherapy. Immunotherapy 2010 2, N 1:57–68.
[4] Castiello L., Sabatino M., Jin P., Clayberger C., Marincola F. M., Krensky A. M., Stroncek D. F. Monocyte-derived DC maturation strategies and related pathways: a transcriptional view. Cancer Immunol. Immunother 2011 60, N 4:457–466.
[5] Jeras M., Bergant M., Repnik U. In vitro preparation and functional assessment of human monocyte-derived dendritic cells-potential antigen-specific modulators of in vivo immune responses. Transpl. Immunol 2005 14, N 3–4:231–244.
[6] Gilboa E. DC-based cancer vaccines. J. Clin. Invest 2007 117, N 5:1195–1203.
[7] Jensen S. S., Gad M. Differential induction of inflammatory cytokines by dendritic cells treated with novel TLR-agonist and cytokine based cocktails: targeting dendritic cells in autoimmunity. J. Inflamm. (Lond) 2010 7:37–48.
[8] Seya T., Akazawa T., Tsujita T., Matsumoto M. Role of Toll-like receptors in adjuvant-augmented immune therapies. eCAM 2006 3, N 1:133–137.
[9] Hemmi H., Akira S. TLR signalling and the function of dendritic cells. Chem. Immunol. Allergy 2005 86:120–135.
[10] Sato A., Iwasaki A. Induction of antiviral immunity requires Toll-like receptor signaling in both stromal and dendritic cell compartments. Proc. Natl Acad. Sci. USA 2004 101, N 46:1624–1629.
[11] Boullart A. C., Aarntzen E. H., Verdijk P., Jacobs J. F., Schuurhuis D. H., Benitez-Ribas D., Schreibelt G., van de Rakt M. W., Scharenborg N. M., de Boer A., Kramer M., Figdor C. G., Punt C. J., Adema G. J., de Vries I. J. Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8 ligands combined with prostaglandin E2 results in high interleukin-12 production and cell migration. Cancer Immunol. Immunother 2008 57, N 11:1589–1597.
[12] Nguyen-Pham T. N., Lim M. S., Nguyen T. A., Lee Y. K., Jin C. J., Lee H. J., Hong C. Y., Ahn J. S., Yang D. H., Kim Y. K., Chung I. J., Park B. C., Kim H. J., Lee J. J. Type I and II interferons enhance dendritic cell maturation and migration capacity by regulating CD38 and CD74 that have synergistic effects with TLR agonists. Cell. Mol. Immunol 2011 8, N 4:341–347.
[13] Warger T., Osterloh P., Rechtsteiner G., Fassbender M., Heib V., Schmid B., Schmitt E., Schild H., Radsak M. P. Synergistic activation of dendritic cells by combined Toll-like receptor ligation induces superior CTL responses in vivo. Blood 2006 108, N 2:544–550.
[14] Krummen M., Balkow S., Shen L., Heinz S., Loquai C., Probst H., Grabbe S. Release of IL-12 by dendritic cells activated by TLR ligation is dependent on MyD88 signaling, whereas TRIF signaling is indispensable for TLR synergy. J. Leukoc. Biol 2010 88, N 1:189–199.
[15] Khranovska N. Preparation strategy and therapeutic application results of a new generation autological dendritic cell-based anticancer vaccine. Oncology (Special issue) 2010 12, N 1 (43) P. 134–139.
[16] Khranovska N. M., Grinevich Yu. A. Preparation method of autological dendritic cell-based anticancer vaccines. Methodological recommendation Kyiv: Naukova dumka, 2006 8 p.
[17] Potebnya G. P., Skivka L. M., Pozur V. V., Rudik M. P., Senchilo N. V., Fedorchuk O. G., Khranovska N. M. Influence of teichoic acid from S. aureus on metabolic activity of macrophages and cytotoxic activity of splenocytes of mice bearing Lewis lung carcinoma. Exp. Oncol 2008 30, N 3 P. 220–223.
[18] Skivka L. M., Trompak O. O., Kudryavets Y. I., Bezdenezhnykh N. A., Susak Y. M. The effect of NSC-631570 (Ukrain) alone and in combination with pathogen-associated molecules on cell cycle distribution and apoptosis induction of mouse melanoma cells with different biological properties. Exp. Oncol 2010 32, N 2:92–96.
[19] Pozur V. The effect of teichoic acid from Staphylococcus aureus Wood 46 on the dendritic cells maturation in vitro. Microbiol. Biotechnol 2010 4, N 12:66–72.
[20] Kim H. S., Shin T. H., Yang S. R., Seo M. S., Kim D. J., Kang S. K., Park J. H., Kang K. S. Implication of NOD1 and NOD2 for the differentiation of multipotent mesenchymal stem cells derived from human umbilical cord blood. PLoS One 2010 5, N 10:15369.
[21] Franchi L., Park J. H., Shaw M. H., Marina-Garcia N., Chen G., Kim Y. G., Nunez G. Intracellular NOD-like receptors in innate immunity, infection and disease. Cell. Microbiol 2008 10, N 1:1–8.
[22] Kaisho T., Akira S. Regulation of dendritic cell function through Toll-like receptors. Curr. Mol. Med 2003 3, N 4:373– 385.
[23] Jin P., Han T. H., Ren .J, Saunders S., Wang E., Marincola F. M., Stroncek D. F. Molecular signatures of maturing dendritic cells: implications for testing the quality of dendritic cell therapies. J. Transl. Med 2010 8:4–18.
[24] Brenner D., Krammer P. H., Arnold R. Concepts of activated T cell death. Crit. Rev. Oncol. Hematol 2008 66, N 1:52–64.