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Changes of Cytokine and Chemokine mRNA Expression in Whole Blood Cells from Active Pulmonary Tuberculosis Patients after T-Cell Mitogen and Mycobacterium tuberculosis Specific Antigen Stimulation

  • Kim, Sunghyun (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Park, Sangjung (Department of Clinical Laboratory Science, College of Medical Science, Daegu Haany University) ;
  • Lee, Hyeyoung (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University)
  • Received : 2014.06.25
  • Accepted : 2014.09.17
  • Published : 2014.09.30

Abstract

Tuberculosis (TB) is one of the major global health problems and it has been estimated that in 5~10% of Mycobacterium tuberculosis (MTB)-infected individuals, the infection progresses to an active disease. Numerous cytokines and chemokines regulate immunological responses at cellular level including stimulation and recruitment of wide range of cells in immunity and inflammation. In the present study, the mRNA expression levels of eight host immune markers containing of IFN-${\gamma}$, TNF-${\alpha}$, IL-2R, IL-4, IL-10, CXCL9, CXCL10, and CXCL11 in whole blood cells from active pulmonary TB patients were measured after T-cell mitogen (PHA) and MTB specific antigens (ESAT-6, CFP-10, and TB7.7). Among the TH1-type factors, IFN-${\gamma}$ mRNA expression was peaked at 4 h, TNF-${\alpha}$ and IL-2R mRNA expression was significantly high at the late time points (24 h) in active TB patients, TH2-type cytokine (IL4 and IL10) mRNA expression levels in both active TB and healthy controls samples did not changed significantly, and the mRNA expression of the three IFN-${\gamma}$-induced chemokines (CXCL9, CXCL10, and CXCL11) were peaked at the late time points (24 h) in active TB patients after MTB specific antigen stimulation. In conclusion, the mRNA expression patterns of the TB-related immune markers in response to the T-cell mitogen (PHA) differed from those in response to MTB specific antigens and these findings may helpful for understanding the relationship between MTB infection and host immune markers in a transcripts level.

Keywords

References

  1. Adane M, Markos A. Cytokines and Chemokines as Biomarkers of Tuberculosis. J Mycobac Dis. 2013. 3: 1-4.
  2. Azzurri A, Sow OY, Amedei A, Bah B, Diallo S. IFN-gamma inducible protein 10 and pentraxin 3 plasma levels are tools for monitoring inflammation and disease activity in Mycobacterium tuberculosis infection. Microbes Infect. 2005. 7: 1-8. https://doi.org/10.1016/j.micinf.2004.09.004
  3. Behr MA, Wilson MA, Gill WP, Salamon H, Schoolnik GK, Rane S, Small PM. Comparative genomics of BCG vaccines by whole genome DNA microarray. Science. 1999. 284: 1520-1523. https://doi.org/10.1126/science.284.5419.1520
  4. Brosch R, Gordon SV, Marmiesse M, Brodin P, Buchrieser C, Eiglmeier K, Garnier T, Gutierrez C, Hewinson G, Kremer K, Parsons LM, Pym AS, Samper S, Soolingen D van, Cole ST. A new evolutionary scenario for the Mycobacterium tuberculosis complex. Proc Natl Acad Sci USA. 2002. 99: 3684-3689. https://doi.org/10.1073/pnas.052548299
  5. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon VS, Eiglmeier K, Gas S, Barry III CE, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998. 393: 537-544. https://doi.org/10.1038/31159
  6. Comstock GW, Livesay VT, Woolpert SF. The prognosis of a positive tuberculin reaction in childhood and adolescence. Am J Epidemiol. 1974. 99: 131-138. https://doi.org/10.1093/oxfordjournals.aje.a121593
  7. Dlugovitzky D, Bay ML, Rateni L, Urizar L, Rondelli CF. In vitro synthesis of interferon-gamma, interleukin-4, transforming growth factor-beta and interleukin-1 beta by peripheral blood mononuclear cells from tuberculosis patients: relationship with the severity of pulmonary involvement. Scand J Immunol. 1999. 49: 210-217. https://doi.org/10.1046/j.1365-3083.1999.00492.x
  8. Dye CS, Schelle P, Dolin V, Pathania, Raviglione MC. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. JAMA. 1999. 282: 677-686. https://doi.org/10.1001/jama.282.7.677
  9. Golden MP, Vikram HR. Extrapulmonary tuberculosis: an overview. Am Fam Physician. 2005. 72: 1761-1768.
  10. Hamelryck TW, Dao-Thi MH, Poortmans F, Chrispeels MJ, Wyns L, Loris R. The crystallographic structure of phytohemagglutinin-L. J of Biol Chem. 1996. 271: 20479-20485. https://doi.org/10.1074/jbc.271.34.20479
  11. Harari A, Rozot V, Enders FB, Perreau M, Stalder JM. Dominant TNF-alpha+ Mycobacterium tuberculosis-specific CD4+ T cell responses discriminate between latent infection and active disease. Nat Med. 2011. 17: 372-376. https://doi.org/10.1038/nm.2299
  12. Juffermans NP, Verbon A, van Deventer SJ. Elevated chemokine concentrations in sera of human immunodeficiency virus (HIV)-seropositive and HIV-seronegative patients with tuberculosis: a possible role for mycobacterial lipoarabinomannan. Infect Immun. 1999. 67: 4295-4297.
  13. Kaplan G, Luster AD, Hancock G, Cohn ZA. The expression of a gamma interferon-induced protein (IP-10) in delayed immune responses in human skin. J Exp Med. 1987. 166: 1098-1108. https://doi.org/10.1084/jem.166.4.1098
  14. Kim S, Kim YK, Lee H, Cho J-E, Kim HY, Uh Y, Kim YM, Kim H, Cho S-N, Jeon B-Y, Lee H. Interferon gamma mRNA quantitative real-time polymerase chain reaction for the diagnosis of latent tuberculosis: a novel interferon gamma release assay. Diagn Microbiol and Infect Dis. 2013. 75: 68-72. https://doi.org/10.1016/j.diagmicrobio.2012.09.015
  15. Lew WT, Lee EG, Kwon DW, Kim SJ, Hong YP, Kim JB. The fate of intractable tuberculosis cases under national tuberculosis programme. Tuberc and Resp Dis. 1995. 42: 11-18. https://doi.org/10.4046/trd.1995.42.1.11
  16. Meher AK, Bal NC, Chary KV, Arora A. Mycobacterium tuberculosis H37Rv ESAT-6-CFP-10 compleand biochemical stability". FEBS J. 2006. 273: 1445-1462. https://doi.org/10.1111/j.1742-4658.2006.05166.x
  17. Okamoto M, Kawabe T, Iwasaki Y. Evaluation of interferongamma, interferon-gamma-inducing cytokines, and interferongamma-inducible chemokines in tuberculous pleural effusions. J Lab Clin Med. 2005. 145: 88-93. https://doi.org/10.1016/j.lab.2004.11.013
  18. Pathak SK, Basu S, Basu KK, Banerjee A, Pathak S, Bhattacharyya A, Kaisho T, Kundu M, Basu J. Direct extracellular interaction between the early secreted antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in macrophages. Nat Immunol. 2007. 8: 610-618. https://doi.org/10.1038/ni1468
  19. Renshaw PS, Lightbody KL, Veverka V, Muskett FW, Kelly G, Frenkiel TA, Gordon SV, Hewinson RG, Burke B, Norman J, Williamson RA, Carr MD. Structure and function of the complex formed by the tuberculosis virulence factors CFP-10 and ESAT-6. EMBO J. 2005. 24: 2491-2498. https://doi.org/10.1038/sj.emboj.7600732
  20. Ulrichs T, Munk ME, Mollenkopf H, Behr-Perst S, Colangeli R. Differential T cell responses to Mycobacterium tuberculosis ESAT6 in tuberculosis patients and healthy controls. Eur J Immunol. 1998. 28: 3949-3958. https://doi.org/10.1002/(SICI)1521-4141(199812)28:12<3949::AID-IMMU3949>3.0.CO;2-4
  21. Walzl G, Ronacher K, Hanekom W, Scriba TJ, Zumla A. Immunological biomarkers of tuberculosis. Nat Rev Immunol. 2011. 11: 343-354. https://doi.org/10.1038/nri2960