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Mycobacterium abscessus MAB2560 induces maturation of dendritic cells via Toll-like receptor 4 and drives Th1 immune response

  • Received : 2014.01.02
  • Accepted : 2014.03.14
  • Published : 2014.09.30

Abstract

In this study, we showed that Mycobacterium abscessus MAB2560 induces the maturation of dendritic cells (DCs), which are representative antigen-presenting cells (APCs). M. abscessus MAB2560 stimulate the production of pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-${\alpha}$, IL-$1{\beta}$, and IL-12p70] and reduce the endocytic capacity and maturation of DCs. Using $TLR4^{-/-}$ DCs, we found that MAB2560 mediated DC maturation via Toll-like receptor 4 (TLR4). MAB2560 also activated the MAPK signaling pathway, which was essential for DC maturation. Furthermore, MAB2560-treated DCs induced the transformation of $na\ddot{i}ve$ T cells to polarized $CD4^+$ and $CD8^+$ T cells, which would be crucial for Th1 polarization of the immune response. Taken together, our results indicate that MAB2560 could potentially regulate the host immune response to M. abscessus and may have critical implications for the manipulation of DC functions for developing DC-based immunotherapy.

Keywords

Dendritic cells;MAB2560;MAPKs;Mycobacterium abscessus;Th1 polarization

References

  1. Banchereau, J. and Steinman, R. M. (1998) Dendritic cells and the control of immunity. Nature 392, 245-252. https://doi.org/10.1038/32588
  2. Janeway, C. A., Jr. and Medzhitov, R. (1998) Introduction: the role of innate immunity in the adaptive immune response. Semin. Immunol. 10, 349-350. https://doi.org/10.1006/smim.1998.0142
  3. Falkinham, J. O., 3rd (2002) Nontuberculous mycobacteria in the environment. Clin. Chest. Med. 23, 529-551. https://doi.org/10.1016/S0272-5231(02)00014-X
  4. Griffith, D. E., Aksamit, T., Brown-Elliott, B. A., Catanzaro, A., Daley, C., Gordin, F., Holland, S. M., Horsburgh, R., Huitt, G., Iademarco, M. F., Iseman, M., Olivier, K., Ruoss, S., von Reyn, C. F., Wallace, R. J., Jr. and Winthrop, K. (2007) An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am. J. Respir. Crit. Care. Med. 175, 367-416. https://doi.org/10.1164/rccm.200604-571ST
  5. Horsburgh, C. R., Jr. and Selik, R. M. (1989) The epidemiology of disseminated nontuberculous mycobacterial infection in the acquired immunodeficiency syndrome (AIDS). Am. Rev. Respir. Dis. 139, 4-7. https://doi.org/10.1164/ajrccm/139.1.4
  6. Brown-Elliott, B. A. and Wallace, R. J., Jr. (2002) Clinical and taxonomic status of pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria. Clin. Microbiol. Rev. 15, 716-746. https://doi.org/10.1128/CMR.15.4.716-746.2002
  7. Shin, D. M., Yang, C. S., Yuk, J. M., Lee, J. Y., Kim, K. H., Shin, S. J., Takahara, K., Lee, S. J. and Jo, E. K. (2008) Mycobacterium abscessus activates the macrophage innate immune response via a physical and functional interaction between TLR2 and dectin-1. Cell Microbiol. 10, 1608-1621. https://doi.org/10.1111/j.1462-5822.2008.01151.x
  8. Agrawal, S., Agrawal, A., Doughty, B., Gerwitz, A., Blenis, J., Van Dyke, T. and Pulendran, B. (2003) Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J. Immunol. 171, 4984-4989. https://doi.org/10.4049/jimmunol.171.10.4984
  9. Noss, E. H., Pai, R. K., Sellati, T. J., Radolf, J. D., Belisle, J., Golenbock, D. T., Boom, W. H. and Harding, C. V. (2001) Toll-like receptor 2-dependent inhibition of macrophage class II MHC expression and antigen processing by 19-kDa lipoprotein of Mycobacterium tuberculosis. J. Immunol. 167, 910-918. https://doi.org/10.4049/jimmunol.167.2.910
  10. Pecora, N. D., Gehring, A. J., Canaday, D. H., Boom, W. H. and Harding, C. V. (2006) Mycobacterium tuberculosis LprA is a lipoprotein agonist of TLR2 that regulates innate immunity and APC function. J. Immunol. 177, 422-429. https://doi.org/10.4049/jimmunol.177.1.422
  11. Gehring, A. J., Dobos, K. M., Belisle, J. T., Harding, C. V. and Boom, W. H. (2004) Mycobacterium tuberculosis LprG (Rv1411c): a novel TLR-2 ligand that inhibits human macrophage class II MHC antigen processing. J. Immunol. 173, 2660-2668. https://doi.org/10.4049/jimmunol.173.4.2660
  12. Quesniaux, V. J., Nicolle, D. M., Torres, D., Kremer, L., Guerardel, Y., Nigou, J., Puzo, G., Erard, F. and Ryffel, B. (2004) Toll-like receptor 2 (TLR2)-dependent-positive and TLR2-independent-negative regulation of proinflammatory cytokines by mycobacterial lipomannans. J. Immunol. 172, 4425-4434. https://doi.org/10.4049/jimmunol.172.7.4425
  13. Jones, B. W., Means, T. K., Heldwein, K. A., Keen, M. A., Hill, P. J., Belisle, J. T. and Fenton, M. J. (2001) Different Toll-like receptor agonists induce distinct macrophage responses. J. Leukoc. Biol. 69, 1036-1044.
  14. Gilleron, M., Quesniaux, V. F. and Puzo, G. (2003) Acylation state of the phosphatidylinositol hexamannosides from Mycobacterium bovis bacillus Calmette Guerin and mycobacterium tuberculosis H37Rv and its implication in Toll-like receptor response. J. Biol. Chem. 278, 29880-29889. https://doi.org/10.1074/jbc.M303446200
  15. Bansal, K., Elluru, S. R., Narayana, Y., Chaturvedi, R., Patil, S. A., Kaveri, S. V., Bayry, J. and Balaji, K. N. (2010) PE_PGRS antigens of Mycobacterium tuberculosis induce maturation and activation of human dendritic cells. J. Immunol. 184, 3495-3504. https://doi.org/10.4049/jimmunol.0903299
  16. Jung, I. D., Jeong, S. K., Lee, C. M., Noh, K. T., Heo, D. R., Shin, Y. K., Yun, C. H., Koh, W. J., Akira, S., Whang, J., Kim, H. J., Park, W. S., Shin, S. J. and Park, Y. M. (2011) Enhanced efficacy of therapeutic cancer vaccines produced by co-treatment with Mycobacterium tuberculosis heparin-binding hemagglutinin, a novel TLR4 agonist. Cancer Res. 71, 2858-2870. https://doi.org/10.1158/0008-5472.CAN-10-3487
  17. Byun, E. H., Kim, W. S., Kim, J. S., Won, C. J., Choi, H. G., Kim, H. J., Cho, S. N., Lee, K., Zhang, T., Hur, G. M. and Shin, S. J. (2012) Mycobacterium paratuberculosis CobT activates dendritic cells via engagement of Toll-like receptor 4 resulting in Th1 cell expansion. J. Biol. Chem. 287, 38609-38624. https://doi.org/10.1074/jbc.M112.391060
  18. Hayashi, F., Smith, K. D., Ozinsky, A., Hawn, T. R., Yi, E. C., Goodlett, D. R., Eng, J. K., Akira, S., Underhill, D. M. and Aderem, A. (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410, 1099-1103. https://doi.org/10.1038/35074106
  19. Sampaio, E. P., Elloumi, H. Z., Zelazny, A., Ding, L., Paulson, M. L., Sher, A., Bafica, A. L., Shea, Y. R. and Holland, S. M. (2008) Mycobacterium abscessus and M. avium trigger Toll-like receptor 2 and distinct cytokine response in human cells. Am. J. Respir. Cell. Mol. Biol. 39, 431-439. https://doi.org/10.1165/rcmb.2007-0413OC
  20. Sim, Y. S., Kim, S. Y., Kim, E. J., Shin, S. J. and Koh, W. J. (2012) Impaired Expression of MAPK Is Associated with the Downregulation of TNF-alpha, IL-6, and IL-10 in Mycobacterium abscessus Lung Disease. Tuberc. Respir. Dis. (Seoul) 72, 275-283. https://doi.org/10.4046/trd.2012.72.3.275
  21. Ordway, D., Henao-Tamayo, M., Smith, E., Shanley, C., Harton, M., Troudt, J., Bai, X., Basaraba, R. J., Orme, I. M. and Chan, E. D. (2008) Animal model of Mycobacterium abscessus lung infection. J. Leukoc. Biol. 83, 1502-1511. https://doi.org/10.1189/jlb.1007696
  22. Vilcek, J., Klion, A., Henriksen-DeStefano, D., Zemtsov, A., Davidson, D. M., Davidson, M., Friedman-Kien, A. E. and Le, J. (1986) Defective gamma-interferon production in peripheral blood leukocytes of patients with acute tuberculosis. J. Clin. Immunol. 6, 146-151. https://doi.org/10.1007/BF00918747
  23. Lee, J. S., Shin, S. J., Collins, M. T., Jung, I. D., Jeong, Y. I., Lee, C. M., Shin, Y. K., Kim, D. and Park, Y. M. (2009) Mycobacterium avium subsp. paratuberculosis fibronectin attachment protein activates dendritic cells and induces a Th1 polarization. Infect. Immun. 77, 2979-2988. https://doi.org/10.1128/IAI.01411-08
  24. Lee, S. J., Noh, K. T., Kang, T. H., Han, H. D., Shin, S. J., Soh, B. Y., Park, J. H., Shin, Y. K., Kim, H. W., Yun, C. H., Park, W. S., Jung, I. D. and Park, Y. M. (2014) The Mycobacterium avium subsp. Paratuberculosis protein MAP1305 modulates dendritic cell-mediated T cell proliferation through Toll-like receptor-4. BMB Rep. 47, 115-120. https://doi.org/10.5483/BMBRep.2014.47.2.277
  25. Noh, K. T., Son, K. H., Jung, I. D., Kang, H. K., Hwang, S. A., Lee, W. S., You, J. C. and Park, Y. M. (2012) Protein kinase C delta (PKCdelta)-extracellular signal-regulated kinase 1/2 (ERK1/2) signaling cascade regulates glycogen synthase kinase-3 (GSK-3) inhibition-mediated interleukin-10 (IL-10) expression in lipopolysaccharide (LPS)-induced endotoxemia. J. Biol. Chem. 287, 14226-14233. https://doi.org/10.1074/jbc.M111.308841

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Acknowledgement

Supported by : Pusan National University