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Molecular Biology Reports

, Volume 39, Issue 3, pp 2157–2162 | Cite as

Aptamer inhibits Mycobacterium tuberculosis (H37Rv) invasion of macrophage

  • Fan Chen
  • XiaoLian Zhang
  • Jing Zhou
  • Shengwu Liu
  • Junyan Liu
Article

Abstract

There is an urgent need to develop new anti-tuberculosis drugs due to the rising tendency in tuberculosis (TB) around the world. It is known that Mycobacterium tuberculosis (M. tuberculosis) generally infects mammalian host via aerosol route. The pathogenic process has been fully studied that it can initially invade alveolar macrophage, then established stable residence within those phagocytic cells, suggesting that one of the possible ways to prevent this pathogen is to inhibit its invasion and growth in the macrophage. Aptamers from SELEX (Systematic Evolution of Ligands by Exponential Enrichment) have been used to rival virulent M. tuberculosis (H37Rv) in our previous work, and the materials to which aptamers bound were proved to be some outer membrane proteins of H37Rv. In the present study, the interaction between M. tuberculosis and macrophage in the presence of aptamers was investigated in more details. The results suggested that the selective aptamers significantly inhibited H37Rv invasion of macrophage in vitro, and the effect correspond to the binding affinity of these aptamers to H37Rv. The values of equilibrium dissociation constant (Kd) was calculated by flow cytometry, all in the nanomolar range, showed much higher affinity to H37Rv than M. bovis Bacillus Guerin (BCG). Moreover, the aptamer-treated H37Rv can stimulate IFN-γ, IL-15 and IL-17 secretion of macrophages compared with H37Rv (no treated). In summary, our data indicated that the NK2 aptamer not only acted as anti-tuberculosis agent by inhibiting virulent M. tuberculosis (H37Rv) invasion of macrophage, but also might be used as molecular probe for exploring the interaction between the outer membrane of M. tuberculosis and macrophage.

Keywords

Aptamer Mycobacterium tuberculosis Macrophage BCG 

References

  1. 1.
    Dye C, Scheele S, Dolin P, Pathania V, Raviglione MC (1999) Consensus statement. Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO global surveillance and monitoring project. JAMA 282:677–686PubMedCrossRefGoogle Scholar
  2. 2.
    Yew WW, Leung CC (2008) Update in tuberculosis 2007. Am J Respir Crit Care Med 177:479–485PubMedCrossRefGoogle Scholar
  3. 3.
    Fine PE (1995) Variation in protection by BCG: implications of and for heterologous immunity. Lancet 346:1339–1345PubMedCrossRefGoogle Scholar
  4. 4.
    Reed SG, Dalemans W, Dalemans W (2003) Prospects for a better vaccine against tuberculosis. Tuberculosis 83:213–219PubMedCrossRefGoogle Scholar
  5. 5.
    Pablos-Mendez A, Raviglione MC, Laszlo A, Binkin N, Rieder HL, Bustreo F, Cohn DL, Lambregts-van Weezenbeek CS, Kim SJ, Chaulet P, Nunn P (1998) Global surveillance for antituberculosis-drug resistance 1994–1997. World Health Organization–International Union against tuberculosis and lung disease working group on anti-tuberculosis drug resistance surveillance. N Engl J Med 338:1641–1649PubMedCrossRefGoogle Scholar
  6. 6.
    Havlir DV, Barnes PF (1999) Current concepts: tuberculosis in patients with human immunodeficiency virus infection. N Engl J Med 340:367–373PubMedCrossRefGoogle Scholar
  7. 7.
    Cohen T, Lipsitch M, Walensky RP, Murray M (2006) Beneficial and perverse effects of isoniazid preventive therapy for latent tuberculosis infection in HIV-tuberculosis coinfected populations. Proc Natl Acad Sci USA 103:7042–7047PubMedCrossRefGoogle Scholar
  8. 8.
    Aaron L, Saadoun D, Calatroni I, Launay O, Memain N, Vincent V, Marchal G, Dupont B, Bouchaud O, Valeyre D, Lortholay O (2004) Tuberculosis in HIV-infected patients: a comprehensive review. Clin Microbiol Infect 10:388–398PubMedCrossRefGoogle Scholar
  9. 9.
    Brennan PJ, Nikaido H (1995) The envelope of mycobacteria. Annu Rev Biochem 64:29–63PubMedCrossRefGoogle Scholar
  10. 10.
    Niederweis M, Danilchanka O, Huff J, Hoffmann C, Engelhardt H (2009) Mycobacterial outer membranes: in search of proteins. Trends Microbiol 18:109–116CrossRefGoogle Scholar
  11. 11.
    Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249:505–510PubMedCrossRefGoogle Scholar
  12. 12.
    Chen CH, Chernis GA, Hoang VQ, Landgraf R (2003) Inhibition of heregulin signaling by an aptamer that preferentially binds to the oligomeric form of human epidermal growth factor receptor-3. Proc Natl Acad Sci USA 100:9226–9231PubMedCrossRefGoogle Scholar
  13. 13.
    Jeon SH, Kayhan B, Ben-Yedidia T, Arnon R (2004) A DNA aptamer prevents influenza infection by blocking the receptor binding region of the viral hemagglutinin. J Biol Chem 279:48410–48419PubMedCrossRefGoogle Scholar
  14. 14.
    Shangguan D, Li Y, Tang Z, Cao ZC, Chen HW, Mallikaratchy P, Sefah K, Wang H, Li Y, Tan W (2006) Aptamers evolved from live cells as effective molecular probes for cancer study. Proc Natl Acad Sci USA 103:11838–11843PubMedCrossRefGoogle Scholar
  15. 15.
    Pan Q, Zhang XL, Wu HY, He PW, Wang FB, Zhang MS, Hu JM, Xia B, Wu JG (2005) Aptamers that preferentially bind type IVB pili and inhibit human monocytic-cell invasion by Salmonella enterica serovar typhi. Antimicrob Agents Chemother 49:4052–4060PubMedCrossRefGoogle Scholar
  16. 16.
    Thiel K (2004) Oligo oligarchy—the surprisingly small world of aptamers. Nat Biotechnol 22:649–651PubMedCrossRefGoogle Scholar
  17. 17.
    Jayasena SD (1999) Aptamers: an emerging class of molecules that rival antibodies in diagnostics. Clin Chem 45:1628–1650PubMedGoogle Scholar
  18. 18.
    Chen F, Zhou J, Luo F, Mohammed A-B, Zhang X-L (2007) Aptamer from whole-bacterium SELEX as new therapeutic reagent against virulent Mycobacterium tuberculosis. Biochem Biophys Res Commun 357:743–748PubMedCrossRefGoogle Scholar
  19. 19.
    McDonough KA, Kress Y, Bloom BR (1993) Pathogenesis of tuberculosis: interaction of M. tuberculosis with macrophages. Infect Immun 61:2763–2773PubMedGoogle Scholar
  20. 20.
    Kaufmann SH (2001) How can immunology contribute to the control of tuberculosis? Nat Rev Immunol 1:20–30PubMedCrossRefGoogle Scholar
  21. 21.
    Russell DG (2001) Mycobacterium tuberculosis: here today, and here tomorrow. Nat Rev Mol Cell Biol 2:569–577PubMedCrossRefGoogle Scholar
  22. 22.
    Adams DO, Hamilton TA (1984) The cell biology of macrophage activation. Annu Rev Immunol 2:283–318PubMedCrossRefGoogle Scholar
  23. 23.
    Fenton MJ, Vermeulen MW, Kim S, Burdick M, Strieter RM, Kornfeld H (1997) Induction of gamma interferon production in human alveolar macrophages by M. tuberculosis. Infect Immun 65:5149–5156PubMedGoogle Scholar
  24. 24.
    Bogdan C, Schleicher U (2006) Production of interferon-gamma by myeloid cells-fact or fancy? Trends Immunol 27:282–290PubMedCrossRefGoogle Scholar
  25. 25.
    Flynn JL, Chan J (2001) Immunology of tuberculosis. Annu Rev Immunol 19:93–129PubMedCrossRefGoogle Scholar
  26. 26.
    Fortune SM, Solache A, Jaeger A, Hill PJ, Belisle JT, Bloom BR, Rubin EJ, Ernst JD (2004) M. tuberculosis inhibits macrophage responses to IFN-gamma through myeloid differentiation factor 88-dependent and -independent mechanisms. J Immunol 172:6272–6280PubMedGoogle Scholar
  27. 27.
    Lazarevic V, Yankura DJ, Divito SJ, Flynn JL (2005) Induction of M. tuberculosis-specific primary and secondary T-cell responses in interleukin-15-deficient mice. Infect Immun 73:2910–2922PubMedCrossRefGoogle Scholar
  28. 28.
    Khader SA, Bell GK, Pearl JE, Fountain JJ, Rangel-Moreno J, Cilley GE (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 8:369–377PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Fan Chen
    • 1
  • XiaoLian Zhang
    • 2
  • Jing Zhou
    • 3
  • Shengwu Liu
    • 2
  • Junyan Liu
    • 2
  1. 1.The Faculty of Life SciencesHubei UniversityWuchangChina
  2. 2.Department of Immunology, State Key Laboratory of Virology, Hubei Province Key Laboratory of Allergy and ImmunologyWuhan University School of MedicineWuhanChina
  3. 3.Wuhan Tuberculosis DispensaryQiaokouChina

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