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Macrophage-Microglia Networks Drive M1 Microglia Polarization After Mycobacterium Infection

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Abstract

Central nervous system tuberculosis (CNS-TB) is caused by infection with Mycobacterium tuberculosis (Mtb). The inflammatory response following CNS-TB involves the activation of resident microglia and the infiltration of macrophages. However, it has not been clarified whether microglia can be polarized into the classically activated proinflammatory M1 phenotype or the alternatively activated anti-inflammatory M2 phenotype after Mtb infection. In this study, we found that BV2 treated with conditioned media from cultures of macrophages infected with Mycobacterium marinum (Mm) induced the expression of M1 phenotypic genes including iNOS, TNF-α, IL-1β, IL-6, CCL2, and CXCL10 but reduced that of M2 phenotypic genes such as Arginase 1, Ym1, and CD163. These results suggest that polarization of microglia is partly mediated through macrophage-microglia interactions as a priming signal. Overall, these results provide new insights into the modulatory mechanisms of microglial polarization, thereby possibly facilitating the development of new therapies for CNS-TB infection via the regulation of microglial polarization through signalling derived from macrophages infected with mycobacteria.

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References

  1. Kingkaew, N., B. Sangtong, W. Amnuaiphon, J. Jongpaibulpatana, W. Mankatittham, S. Akksilp, C. Sirinak, S. Nateniyom, C. Burapat, W. Kittikraisak, P. Monkongdee, and J.K. Varma. 2009. HIV-associated extrapulmonary tuberculosis in Thailand: epidemiology and risk factors for death. International Journal of Infectious Diseases 13: 722–729.

    Article  CAS  PubMed  Google Scholar 

  2. DeLance, A.R., M. Safaee, M.C. Oh, A.J. Clark, G. Kaur, M.Z. Sun, A.W. Bollen, J.J. Phillips, and A.T. Parsa. 2013. Tuberculoma of the central nervous system. Journal of Clinical Neuropsychology 20: 1333–1341.

    Google Scholar 

  3. Donald, P.R., H.S. Schaaf, and J.F. Schoeman. 2005. Tuberculous meningitis and miliary tuberculosis: the rich focus revisited. The Journal of Infection 50: 193–195.

    Article  CAS  PubMed  Google Scholar 

  4. Jain, S.K., M. Paul-Satyaseela, G. Lamichhane, K.S. Kim, and W.R. Bishai. 2006. Mycobacterium tuberculosis invasion and traversal across an in vitro human blood–brain barrier as a pathogenic mechanism for central nervous system tuberculosis. The Journal of Infectious Diseases 193: 1287–1295.

    Article  CAS  PubMed  Google Scholar 

  5. van Leeuwen, L. M., M. van der Kuip, S. A. Youssef, A. de Bruin, W. Bitter, A. M. van Furth, and A. M. van der Sar. 2014. Modelling tuberculous meningitis in zebrafish using Mycobacterium marinum. Dis Model Mech.

  6. Mosser, D.M., and J.P. Edwards. 2008. Exploring the full spectrum of macrophage activation. Nature Reviews Immunology 8: 958–969.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Benoit, M., B. Desnues, and J.L. Mege. 2008. Macrophage polarization in bacterial infections. Journal of Immunology 181: 3733–3739.

    Article  CAS  Google Scholar 

  8. Taylor, P.R., L. Martinez-Pomares, M. Stacey, H.H. Lin, G.D. Brown, and S. Gordon. 2005. Macrophage receptors and immune recognition. Annual Review of Immunology 23: 901–944.

    Article  CAS  PubMed  Google Scholar 

  9. MacMicking, J., Q.W. Xie, and C. Nathan. 1997. Nitric oxide and macrophage function. Annual Review of Immunology 15: 323–350.

    Article  CAS  PubMed  Google Scholar 

  10. Rock, R.B., S. Hu, G. Gekker, W.S. Sheng, B. May, V. Kapur, and P.K. Peterson. 2005. Mycobacterium tuberculosis-induced cytokine and chemokine expression by human microglia and astrocytes: effects of dexamethasone. The Journal of Infectious Diseases 192: 2054–2058.

    Article  CAS  PubMed  Google Scholar 

  11. Rock, R.B., M. Olin, C.A. Baker, T.W. Molitor, and P.K. Peterson. 2008. Central nervous system tuberculosis: pathogenesis and clinical aspects. Clinical Microbiology Reviews 21: 243–261.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Mills, C.D., K. Kincaid, J.M. Alt, M.J. Heilman, and A.M. Hill. 2000. M-1/M-2 macrophages and the Th1/Th2 paradigm. Journal of Immunology 164: 6166–6173.

    Article  CAS  Google Scholar 

  13. Lacy-Hulbert, A., and K.J. Moore. 2006. Designer macrophages: oxidative metabolism fuels inflammation repair. Cell Metabolism 4: 7–8.

    Article  CAS  PubMed  Google Scholar 

  14. Durafourt, B.A., C.S. Moore, D.A. Zammit, T.A. Johnson, F. Zaguia, M.C. Guiot, A. Bar-Or, and J.P. Antel. 2012. Comparison of polarization properties of human adult microglia and blood-derived macrophages. Glia 60: 717–727.

    Article  PubMed  Google Scholar 

  15. Perry, V.H., and J. Teeling. 2013. Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration. Seminars in Immunopathology 35: 601–612.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Tobin, D.M., and L. Ramakrishnan. 2008. Comparative pathogenesis of mycobacterium marinum and mycobacterium tuberculosis. Cellular Microbiology 10: 1027–1039.

    Article  CAS  PubMed  Google Scholar 

  17. Mishra, B.B., V.A. Rathinam, G.W. Martens, A.J. Martinot, H. Kornfeld, K.A. Fitzgerald, and C.M. Sassetti. 2013. Nitric oxide controls the immunopathology of tuberculosis by inhibiting NLRP3 inflammasome-dependent processing of IL-1beta. Nature Immunology 14: 52–60.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Saura, J., J.M. Tusell, and J. Serratosa. 2003. High-yield isolation of murine microglia by mild trypsinization. Glia 44: 183–189.

    Article  PubMed  Google Scholar 

  19. Dong, D., D. Wang, M. Li, H. Wang, J. Yu, C. Wang, J. Liu, and Q. Gao. 2012. PPE38 modulates the innate immune response and is required for mycobacterium marinum virulence. Infection and Immunity 80: 43–54.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Green, J.A., P.T. Elkington, C.J. Pennington, F. Roncaroli, S. Dholakia, R.C. Moores, A. Bullen, J.C. Porter, D. Agranoff, D.R. Edwards, and J.S. Friedland. 2010. Mycobacterium tuberculosis upregulates microglial matrix metalloproteinase-1 and -3 expression and secretion via NF-kappaB- and activator protein-1-dependent monocyte networks. Journal of Immunology 184: 6492–6503.

    Article  CAS  Google Scholar 

  21. Lee, H.M., J. Kang, S.J. Lee, and E.K. Jo. 2013. Microglial activation of the NLRP3 inflammasome by the priming signals derived from macrophages infected with mycobacteria. Glia 61: 441–452.

    Article  PubMed  Google Scholar 

  22. Hickey, W.F. 2001. Basic principles of immunological surveillance of the normal central nervous system. Glia 36: 118–124.

    Article  CAS  PubMed  Google Scholar 

  23. Isabel, B.E., and H.P. Rogelio. 2014. Pathogenesis and immune response in tuberculous meningitis. Malays Journal of Medical Sciences 21: 4–10.

    Google Scholar 

  24. Moens, L., G. Wuyts, L. Boon, M.T. den Hartog, J.L. Ceuppens, and X. Bossuyt. 2008. The human polysaccharide- and protein-specific immune response to Streptococcus pneumoniae is dependent on CD4 (+) T lymphocytes, CD14 (+) monocytes, and the CD40-CD40 ligand interaction. The Journal of Allergy and Clinical Immunology 122: 1231–1233.

    Article  CAS  PubMed  Google Scholar 

  25. Colton, C., and D.M. Wilcock. 2010. Assessing activation states in microglia. CNS & Neurological Disorders Drug Targets 9: 174–191.

    Article  CAS  Google Scholar 

  26. Bogdan, C. 2001. Nitric oxide and the immune response. Nature Immunology 2: 907–916.

    Article  CAS  PubMed  Google Scholar 

  27. Chan, J., Y. Xing, R.S. Magliozzo, and B.R. Bloom. 1992. Killing of virulent mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages. The Journal of Experimental Medicine 175: 1111–1122.

    Article  CAS  PubMed  Google Scholar 

  28. Chacon-Salinas, R., J. Serafin-Lopez, R. Ramos-Payan, P. Mendez-Aragon, R. Hernandez-Pando, D. Van Soolingen, L. Flores-Romo, S. Estrada-Parra, and I. Estrada-Garcia. 2005. Differential pattern of cytokine expression by macrophages infected in vitro with different Mycobacterium tuberculosis genotypes. Clinical and Experimental Immunology 140: 443–449.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Raju, B., Y. Hoshino, I. Belitskaya-Levy, R. Dawson, S. Ress, J.A. Gold, R. Condos, R. Pine, S. Brown, A. Nolan, W.N. Rom, and M.D. Weiden. 2008. Gene expression profiles of bronchoalveolar cells in pulmonary TB. Tuberculosis (Edinburgh, Scotland) 88: 39–51.

    Article  CAS  Google Scholar 

  30. Kiszewski, A.E., E. Becerril, L.D. Aguilar, I.T. Kader, W. Myers, F. Portaels, and P.R. Hernandez. 2006. The local immune response in ulcerative lesions of Buruli disease. Clinical and Experimental Immunology 143: 445–451.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Murphy, J.T., S. Sommer, E.A. Kabara, N. Verman, M.A. Kuelbs, P. Saama, R. Halgren, and P.M. Coussens. 2006. Gene expression profiling of monocyte-derived macrophages following infection with mycobacterium avium subspecies avium and mycobacterium avium subspecies paratuberculosis. Physiological Genomics 28: 67–75.

    Article  CAS  PubMed  Google Scholar 

  32. Gordon, S. 2003. Alternative activation of macrophages. Nature Reviews Immunology 3: 23–35.

    Article  CAS  PubMed  Google Scholar 

  33. Lugo-Villarino, G., D. Hudrisier, A. Benard, and O. Neyrolles. 2012. Emerging trends in the formation and function of tuberculosis granulomas. Frontiers in Immunology 3: 405.

    PubMed Central  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant numbers: 81201252, 81373223, 31100112), a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), a project funded by the Scientific Research Programme of Nantong (HS2012059, BK2014033); and a project funded by the Natural Scientific Research Programme of Jiangsu Province (14KJD180002).

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Authors and Affiliations

  1. Department of Pathogen and Immunology, Medical College, Nantong University, 19 Qixiu Road, Nantong, 226001, Jiangsu, People’s Republic of China

    Yongwei Qin, Xiaolei Sun, Xiaoyi Shao, Chun Cheng, Jinrong Feng, Wei Sun, Wei Liu & Yinong Duan

  2. The Sixth People’s Hospital of Nantong, 500 Yonghe Road, Nantong, 226011, China

    Delin Gu & Feifan Xu

Authors
  1. Yongwei Qin
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  2. Xiaolei Sun
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  3. Xiaoyi Shao
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  4. Chun Cheng
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  5. Jinrong Feng
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  6. Wei Sun
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  7. Delin Gu
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  8. Wei Liu
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  10. Yinong Duan
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Correspondence to Yinong Duan.

Additional information

Yongwei Qin and Xiaolei Sun contributed equally to this work.

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Qin, Y., Sun, X., Shao, X. et al. Macrophage-Microglia Networks Drive M1 Microglia Polarization After Mycobacterium Infection. Inflammation 38, 1609–1616 (2015). https://doi.org/10.1007/s10753-015-0136-y

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