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Characterization of Th1- and Th2-type immune response in human multidrug-resistant tuberculosis

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Abstract

Multidrug-resistant tuberculosis (MDR-TB) has become a lethal global threat. Insights into the immune regulation of MDR-TB are urgently needed for the development of new treatments; however, the T cell response to an MDR-TB infection in human remains unclear. In the present study, the proportion of Th1 and Th2 cell subsets and the level of related T cell subset cytokines in peripheral blood were investigated. We detected that an MDR-TB infection resulted in suppressed Th1 and Th2 cell activation, which was more remarkable in patients with MDR-TB than that in drug-sensitive tuberculosis (DS-TB) sufferers when compared to healthy controls (HCs). In addition, MDR-TB infection down-regulated the expression of IFN-γ, IL-2, and IL-10, and up-regulated IL-4, IL-6, and TNF-α expression. Our data suggest that the disturbance between protective and pathogenic effects induced by the immunosuppression of Th1- and Th2-type responses is a substantial characteristic of MDR-TB infections.

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References

  1. Kant S, Maurya AK, Kushwaha RA, Nag VL, Prasad R (2010) Multi-drug resistant tuberculosis: an iatrogenic problem. Biosci Trends 4:48–55

    PubMed  Google Scholar 

  2. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136:2348–2357

    PubMed  CAS  Google Scholar 

  3. Flynn JL, Chan J (2001) Immunology of tuberculosis. Annu Rev Immunol 19:93–129

    Article  PubMed  CAS  Google Scholar 

  4. Demangel C, Britton WJ (2000) Interaction of dendritic cells with mycobacteria: where the action starts. Immunol Cell Biol 78:318–324

    Article  PubMed  CAS  Google Scholar 

  5. Rengarajan J, Szabo SJ, Glimcher LH (2000) Transcriptional regulation of Th1/Th2 polarization. Immunol Today 21:479–483

    Article  PubMed  CAS  Google Scholar 

  6. Gor DO, Rose NR, Greenspan NS (2003) TH1–TH2: a procrustean paradigm. Nat Immunol 4:503–505

    Article  PubMed  CAS  Google Scholar 

  7. Bai X, Wilson SE, Chmura K, Feldman NE, Chan ED (2004) Morphometric analysis of Th(1) and Th(2) cytokine expression in human pulmonary tuberculosis. Tuberculosis (Edinb) 84:375–385

    Article  Google Scholar 

  8. Infante-Duarte C, Kamradt T (1999) Th1/Th2 balance in infection. Springer Semin Immunopathol 21:317–338

    Article  PubMed  CAS  Google Scholar 

  9. Domínguez J, De Souza-Galvão M, Ruiz-Manzano J, Latorre I, Prat C, Lacoma A, Milà C, Jiménez MA, Blanco S, Maldonado J, Altet N, Ausina V (2009) T-cell responses to the Mycobacterium tuberculosis-specific antigens in active tuberculosis patients at the beginning, during, and after antituberculosis treatment. Diagn Microbiol Infect Dis 63:43–51

    Article  PubMed  Google Scholar 

  10. Wang D, Yang C, Kuang T, Lei H, Meng X, Tong A, He J, Jiang Y, Guo F, Dong M (2010) Prevalence of multidrug and extensively drug-resistant tuberculosis in Beijing, China: a hospital-based retrospective study. Jpn J Infect Dis 63:368–371

    PubMed  Google Scholar 

  11. Lucey DR, Clerici M, Shearer GM (1996) Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clin Microbiol Rev 9:532–562

    PubMed  CAS  Google Scholar 

  12. Sharma SK, Mitra DK, Balamurugan A, Pandey RM, Mehra NK (2002) Cytokine polarization in miliary and pleural tuberculosis. J Clin Immunol 22:345–352

    Article  PubMed  CAS  Google Scholar 

  13. Fenhalls G, Stevens L, Bezuidenhout J, Amphlett GE, Duncan K, Bardin P, Lukey PT (2002) Distribution of IFN-gamma, IL-4 and TNF-alpha protein and CD8 T cells producing IL-12p40 mRNA in human lung tuberculous granulomas. Immunology 105:325–335

    Article  PubMed  CAS  Google Scholar 

  14. Flynn JL, Chan J, Triebold KJ, Dalton DK, Stewart TA, Bloom BR (1993) An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med 178:2249–2254

    Article  PubMed  CAS  Google Scholar 

  15. Cooper AM, Dalton DK, Stewart TA, Griffin JP, Russell DG, Orme IM (1993) Disseminated tuberculosis in interferon gamma gene-disrupted mice. J Exp Med 178:2243–2247

    Article  PubMed  CAS  Google Scholar 

  16. Fenton MJ, Vermeulen MW, Kim S, Burdick M, Strieter RM, Kornfeld H (1997) Induction of gamma interferon production in human alveolar macrophages by Mycobacterium tuberculosis. Infect Immun 65:5149–5156

    PubMed  CAS  Google Scholar 

  17. Bergeron A, Bonay M, Kambouchner M, Lecossier D, Riquet M, Soler P, Hance A, Tazi A (1997) Cytokine patterns in tuberculous and sarcoid granulomas: correlations with histopathologic features of the granulomatous response. J Immunol 159:3034–3043

    PubMed  CAS  Google Scholar 

  18. Ruhwald M, Petersen J, Kofoed K, Nakaoka H, Cuevas LE, Lawson L, Squire SB, Eugen-Olsen J, Ravn P (2008) Improving T-cell assays for the diagnosis of latent TB infection: potential of a diagnostic test based on IP-10. PLoS One 3:e2858

    Article  PubMed  Google Scholar 

  19. Biselli R, Mariotti S, Sargentini V, Sauzullo I, Lastilla M, Mengoni F, Vanini V, Girardi E, Goletti D, D’Amelio R, Nisini R (2010) Detection of interleukin-2 in addition to interferon-gamma discriminates active tuberculosis patients, latently infected individuals, and controls. Clin Microbiol Infect 16:1282–1284

    Article  PubMed  CAS  Google Scholar 

  20. Zhang M, Lin Y, Iyer DV, Gong J, Abrams JS, Barnes PF (1995) T-cell cytokine responses in human infection with Mycobacterium tuberculosis. Infect Immun 63:3231–3234

    PubMed  CAS  Google Scholar 

  21. Sodhi A, Gong J, Silva C, Qian D, Barnes PF (1997) Clinical correlates of interferon gamma production in patients with tuberculosis. Clin Infect Dis 25:617–620

    Article  PubMed  CAS  Google Scholar 

  22. Nemeth J, Winkler HM, Boeck L, Adegnika AA, Clement E, Mve TM, Kremsner PG, Winkler S (2010) Specific cytokine patterns of pulmonary tuberculosis in Central Africa. Clin Immunol 138:50–59

    Article  PubMed  CAS  Google Scholar 

  23. Marino S, Myers A, Flynn JL, Kirschner DE (2010) TNF and IL-10 are major factors in modulation of the phagocytic cell environment in lung and lymph node in tuberculosis: a next-generation two-compartmental model. J Theor Biol 265:586–598

    Article  PubMed  CAS  Google Scholar 

  24. Quesniaux VF, Jacobs M, Allie N, Grivennikov S, Nedospasov SA, Garcia I, Olleros ML, Shebzukhov Y, Kuprash D, Vasseur V, Rose S, Court N, Vacher R, Ryffel B (2010) TNF in host resistance to tuberculosis infection. Curr Dir Autoimmun 11:157–179

    Article  PubMed  CAS  Google Scholar 

  25. Hernández-Pando R, Orozcoe H, Sampieri A, Pavón L, Velasquillo C, Larriva-Sahd J, Alcocer JM, Madrid MV (1996) Correlation between the kinetics of Th1, Th2 cells and pathology in a murine model of experimental pulmonary tuberculosis. Immunology 89:26–33

    PubMed  Google Scholar 

  26. Verbon A, Juffermans N, Van Deventer SJ, Speelman P, Van Deutekom H, Van Der Poll T (1999) Serum concentrations of cytokines in patients with active tuberculosis (TB) and after treatment. Clin Exp Immunol 115:110–113

    Article  PubMed  CAS  Google Scholar 

  27. van Crevel R, Karyadi E, Preyers F, Leenders M, Kullberg BJ, Nelwan RH, van der Meer JW (2000) Increased production of interleukin 4 by CD4+ and CD8+ T cells from patients with tuberculosis is related to the presence of pulmonary cavities. J Infect Dis 181:1194–1197

    Article  PubMed  Google Scholar 

  28. Ordway DJ, Costa L, Martins M, Silveira H, Amaral L, Arroz MJ, Ventura FA, Dockrell HM (2004) Increased Interleukin-4 production by CD8 and gammadelta T cells in health-care workers is associated with the subsequent development of active tuberculosis. J Infect Dis 190(4):756–766

    Article  PubMed  CAS  Google Scholar 

  29. Rook GA, Zumla A (2001) Advances in the immunopathogenesis of pulmonary tuberculosis. Curr Opin Pulm Med 7(3):116–123

    Article  PubMed  CAS  Google Scholar 

  30. Seah GT, Rook GA (2001) High levels of mRNA encoding IL-4 in unstimulated peripheral blood mononuclear cells from tuberculosis patients revealed by quantitative nested reverse transcriptase-polymerase chain reaction; correlations with serum IgE levels. Scand J Infect Dis 33(2):106–109

    Article  PubMed  CAS  Google Scholar 

  31. Seah GT, Scott GM, Rook GA (2000) Type 2 cytokine gene activation and its relationship to extent of disease in patients with tuberculosis. J Infect Dis 181(1):385–389

    Article  PubMed  CAS  Google Scholar 

  32. Flynn JL (2004) Immunology of tuberculosis and implications in vaccine development. Tuberculosis (Edinb) 84:93–101

    Article  Google Scholar 

  33. Zhang Y, Broser M, Rom W (1995) Activation of the interleukin 6 gene by Mycobacterium tuberculosis or lipopolysaccharide is mediated by nuclear factors NF IL 6 and NF-kappa B. Proc Natl Acad Sci USA 92:3632

    Article  PubMed  CAS  Google Scholar 

  34. Nagabhushanam V, Solache A, Ting LM, Escaron CJ, Zhang JY, Ernst JD (2003) Innate inhibition of adaptive immunity: Mycobacterium tuberculosis-induced IL-6 inhibits macrophage responses to IFN-gamma. J Immunol 171:4750–4757

    PubMed  CAS  Google Scholar 

  35. Mattos AM, Almeida Cde S, Franken KL, Alves CC, Abramo C, de Souza MA, L’Hotellier M, Alves MJ, Ferreira AP, Oliveira SC, Ottenhoff TH, Teixeira HC (2010) Increased IgG1, IFN-gamma, TNF-alpha and IL-6 responses to Mycobacterium tuberculosis antigens in patients with tuberculosis are lower after chemotherapy. Int Immunol 22:775–782

    Article  PubMed  CAS  Google Scholar 

  36. Boussiotis VA, Tsai EY, Yunis EJ, Thim S, Delgado JC, Dascher CC, Berezovskaya A, Rousset D, Reynes JM, Goldfeld AE (2000) IL-10-producing T cells suppress immune responses in anergic tuberculosis patients. J Clin Invest 105:1317–1325

    Article  PubMed  CAS  Google Scholar 

  37. Handzel ZT, Barak V, Altman Y, Bibi H, Lidgi M, Iancovici-Kidon M, Yassky D, Raz M (2007) Increased Th1 and Th2 type cytokine production in patients with active tuberculosis. Isr Med Assoc J 9:479–483

    PubMed  CAS  Google Scholar 

  38. Flesch IE, Hess JH, Oswald IP, Kaufmann SH (1994) Growth inhibition of Mycobacterium bovis by IFN-gamma stimulated macrophages: regulation by endogenous tumor necrosis factor-alpha and by IL-10. Int Immunol 6:693–700

    Article  PubMed  CAS  Google Scholar 

  39. Saunders BM, Frank AA, Orme IM, Cooper AM (2000) Interleukin-6 induces early gamma interferon production in the infected lung but is not required for generation of specific immunity to Mycobacterium tuberculosis infection. Infect Immun 68:3322–3326

    Article  PubMed  CAS  Google Scholar 

  40. Scriba TJ, Kalsdorf B, Abrahams DA, Isaacs F, Hofmeister J, Black G, Hassan HY, Wilkinson RJ, Walzl G, Gelderbloem SJ, Mahomed H, Hussey GD, Hanekom WA (2008) Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response. J Immunol 180:1962–1970

    PubMed  CAS  Google Scholar 

  41. Khader SA, Cooper AM (2008) IL-23 and IL-17 in tuberculosis. Cytokine 41:79–83

    Article  PubMed  CAS  Google Scholar 

  42. Khader SA, Bell GK, Pearl JE, Fountain JJ, Rangel-Moreno J, Cilley GE, Shen F, Eaton SM, Gaffen SL, Swain SL, Locksley RM, Haynes L, Randall TD, Cooper AM (2007) IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge. Nat Immunol 8:369–377

    Article  PubMed  CAS  Google Scholar 

  43. Annunziato F, Cosmi L, Santarlasci V, Maggi L, Liotta F, Mazzinghi B, Parente E, Filì L, Ferri S, Frosali F, Giudici F, Romagnani P, Parronchi P, Tonelli F, Maggi E, Romagnani S (2007) Phenotypic and functional features of human Th17 cells. J Exp Med 204:1849–1861

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank W. G. Xu for the excellent assistance in the collation of patients and technical advice, and all of the patients and controls who donated the samples.

Funding

Funding for this study was provided by grants from one of the major projects for science and technology development “11th Five-Year Plan” on Key Infectious Diseases of the National Department of Technology (no. 2008ZX10003-014).

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Authors and Affiliations

  1. Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

    Q. Tan, W. P. Xie, R. Min, G. Q. Dai, C.-C. Xu & H. Wang

  2. The Third Hospital of Zhenjiang City, Zhenjiang, China

    H. Q. Pan

  3. Center for Disease Control and Prevention (CDC) of Taizhou City, Taizhou, China

    C. D. Miao

  4. Jiangbei Hospital, Nanjing, China

    Z. Yang

  5. Center for Disease Control and Prevention of Jiangsu Province, Nanjing, China

    W. G. Xu

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  1. Q. Tan
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  9. W. G. Xu
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  10. H. Wang
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Correspondence to H. Wang.

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Tan, Q., Xie, W.P., Min, R. et al. Characterization of Th1- and Th2-type immune response in human multidrug-resistant tuberculosis. Eur J Clin Microbiol Infect Dis 31, 1233–1242 (2012). https://doi.org/10.1007/s10096-011-1434-4

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  • DOI: https://doi.org/10.1007/s10096-011-1434-4

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