1921
  1. Home
  2. The American Journal of Tropical Medicine and Hygiene
  3. Volume 100, Issue 6
  4. Article
Volume 100, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645
Download

Abstract

Abstract.

Lymph node tuberculosis (LNTB) is characterized by the enhanced baseline and antigen-specific production of type 1/17 cytokines and reduced baseline and antigen-specific production of interleukin (IL)-1β and IL-18 at the site of infection when compared with peripheral blood. However, the cytokine profile in the lymph nodes (LNs) of culture–positive LNTB (LNTB+) and negative LNTB (LNTB−) has not been examined. To address this, we have examined the baseline and mycobacterial antigen–stimulated cytokine levels of type 1 (interferon gamma [IFNγ], tumor necrosis factor alpha [TNFα], IL-2), type 2 (IL-4, IL-5, and IL-13), type 17 (IL-17A, IL-17F, and IL-22), pro-inflammatory (IL-1α, IL-1β, IL-18, and granulocyte macrophage colony-stimulating factor [GM-CSF]), and regulatory cytokines (IL-10, transforming growth factor beta [TGF-β]) cytokines in the LN culture supernatants of LNTB+ and LNTB− individuals. We have observed significantly enhanced baseline levels of IL-13 and IL-10 and significantly reduced baseline levels of IL-4 and GM-CSF in LNTB+ individuals compared with LNTB− individuals. By contrast, we have observed significantly enhanced levels of type 1 (IFNγ, TNFα, and IL-2), type 17 (IL-17F and IL-22), and pro-inflammatory (IL-1α and GM-CSF) cytokines and significantly reduced levels of TGFβ in response to purified protein derivative, early secreted antigen-6, and culture filtrate protein-10 antigens in LNTB+ compared with LNTB− individuals. On phorbol 12-myristate 13-acetate/ionomycin stimulation, no significant difference was observed for any of the cytokines examined. Thus, our study revealed several interesting differences in the cytokine profiles of mycobacterial antigen–stimulated LN cultures in LNTB+ and LNTB− individuals. Therefore, we suggest the presence of mycobacteria plays a significant role in driving the cytokine response at the site of infection in LNTB.

© The American Society of Tropical Medicine and Hygiene
Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.18-0834
2019-04-15
2020-10-24

  • From This Site

    /content/journals/10.4269/ajtmh.18-0834
    dcterms_title,dcterms_subject,pub_keyword
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/14761645/100/6/tpmd180834.html?itemId=/content/journals/10.4269/ajtmh.18-0834&mimeType=html&fmt=ahah

References

  1. Sharma SK, Mohan A, 2004. Extrapulmonary tuberculosis. Ind J Med Res 120: 316–353.
     [Google Scholar]
  2. Korea Centers for Disease Control and Prevention, 2014. Annual Report on the Notified Tuberculosis in Korea. Cheongwon, Korea: Korea Centers for Disease Control and Prevention, 2013.
     [Google Scholar]
  3. Gothi D, Jaswal A, Spalgais S, 2016. Lymph node tuberculosis. EC Pulmonol Respir Med 2.5: 194–211.
     [Google Scholar]
  4. Handa U, Mundi I, Mohan S, 2012. Nodal tuberculosis revisited: a review. J Infect Dev Ctries 6: 6–12.
     [Google Scholar]
  5. Knox J, Lane G, Wong JSJ, Trevan PG, Karunajeewa H, 2012. Diagnosis of tuberculous lymphadenitis using fine needle aspiration biopsy. Intern Med J 42: 1029–1036.
     [Google Scholar]
  6. Cooper AM, 2009. Cell-mediated immune responses in tuberculosis. Annu Rev Immunol 27: 393–422.
     [Google Scholar]
  7. Arenas-Ramirez N, Woytschak J, Boyman O, 2015. Interleukin-2: biology, design and application. Trends Immunol 36: 763–777.
     [Google Scholar]
  8. Kolls JK, Khader SA, 2010. The role of Th17 cytokines in primary mucosal immunity. Cytokine Growth Factor Rev 21: 443–448.
     [Google Scholar]
  9. Dudakov JA, Hanash AM, van den Brink MR, 2015. Interleukin-22: immunobiology and pathology. Annu Rev Immunol 33: 747–785.
     [Google Scholar]
  10. O’Garra A, Redford PS, McNab FW, Bloom CI, Wilkinson RJ, Berry MP, 2013. The immune response in tuberculosis. Annu Rev Immunol 31: 475–527.
     [Google Scholar]
  11. Mayer-Barber KD, Sher A, 2015. Cytokine and lipid mediator networks in tuberculosis. Immunol Rev 264: 264–275.
     [Google Scholar]
  12. Rothchild AC, Jayaraman P, Nunes-Alves C, Behar SM, 2014. iNKT cell production of GM-CSF controls Mycobacterium tuberculosis. PLoS Pathog 10: e1003805.
     [Google Scholar]
  13. Griffin JD, Cannistra SA, Sullivan R, Demetri GD, Ernst TJ, Kanakura Y, 1990. The biology of GM-CSF: regulation of production and interaction with its receptor. Int J Cell Cloning 8 (Suppl 1): 35–44; discussion 44–45.
     [Google Scholar]
  14. Ellner JJ, 2010. Immunoregulation in TB: observations and implications. Clin Transl Sci 3: 23–28.
     [Google Scholar]
  15. Bhatt K, Verma S, Ellner JJ, Salgame P, 2015. Quest for correlates of protection against tuberculosis. Clin Vaccine Immunol 22: 258–266.
     [Google Scholar]
  16. Kumar NP, Gopinath V, Sridhar R, Hanna LE, Banurekha VV, Jawahar MS, Nutman TB, Babu S, 2013. IL-10 dependent suppression of type 1, type 2 and type 17 cytokines in active pulmonary tuberculosis. PLoS One 8: e59572.
     [Google Scholar]
  17. Kumar NP, Sridhar R, Banurekha VV, Nair D, Jawahar MS, Nutman TB, Babu S, 2013. Expansion of pathogen-specific mono- and multifunctional Th1 and Th17 cells in multi- focal tuberculous lymphadenitis. PLoS One 8: e57123.
     [Google Scholar]
  18. Kumar NP, Sridhar R, Hanna LE, Banurekha VV, Jawahar MS, Nutman TB, Babu S, 2014. Altered CD8(+) T cell frequency and function in tuberculous lymphadenitis. Tuberculosis (Edinb) 94: 482–493.
     [Google Scholar]
  19. Kathamuthu GR, Moideen K, Bhaskaran D, Sekar G, Sridhar R, Vidyajayanthi B, Gajendraraj G, Babu S, 2017. Reduced systemic and mycobacterial antigen-stimulated concentrations of IL-1β and IL-18 in tuberculous lymphadenitis. Cytokine 90: 66–72.
     [Google Scholar]
  20. Kathamuthu GR et al., 2017. Tuberculous lymphadenitis is associated with enhanced baseline and antigen-specific induction of type 1 and type 17 cytokines and reduced interleukin-1β (IL-1β) and IL-18 at the site of infection. Clin Vaccine Immunol 24: e00045-17.
     [Google Scholar]
  21. Cooper AM, Mayer-Barber KD, Sher A, 2011. A role of innate cytokines in mycobacterial infection. Mucosal Immunol 4: 252–260.
     [Google Scholar]
  22. Sahiratmadja E et al., 2007. Plasma granulysin levels and cellular interferon-gamma production correlate with curative host responses in tuberculosis, while plasma interferon-gamma levels correlate with tuberculosis disease activity in adults. Tuberculosis (Edinb) 87: 312–321.
     [Google Scholar]
  23. 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.
     [Google Scholar]
  24. 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.
     [Google Scholar]
  25. Nandi B, Behar SM, 2011. Regulation of neutrophils by interferon-γ limits lung inflammation during tuberculosis infection. J Exp Med 208: 2251–2262.
     [Google Scholar]
  26. Al-Attiyah R, El-Shazly A, Mustafa AS, 2012. Comparative analysis of spontaneous and mycobacterial antigen-induced secretion of Th1, Th2 and pro-inflammatory cytokines by peripheral blood mononuclear cells of tuberculosis patients. Scand J Immunol 75: 623–632.
     [Google Scholar]
  27. Kumar Nathella P, Babu S, 2017. Influence of diabetes mellitus on immunity to human tuberculosis. Immunology 152: 13–24.
     [Google Scholar]
  28. Millington KA, Gooding S, Hinks TS, Reynolds DJ, Lalvani A, 2010. Mycobacterium tuberculosis-specific cellular immune profiles suggest bacillary persistence decades after spontaneous cure in untreated tuberculosis. J Infect Dis 202: 1685–1689.
     [Google Scholar]
  29. Khader SA et al., 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.
     [Google Scholar]
  30. Jurado JO et al., 2012. IL-17 and IFN-γ expression in lymphocytes from patients with active tuberculosis correlates with the severity of the disease. J Leukoc Biol 91: 991–1002.
     [Google Scholar]
  31. Yang XO et al., 2008. Regulation of inflammatory responses by IL-17F. J Exp Med 205: 1063–1075.
     [Google Scholar]
  32. Scriba TJ et al., 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.
     [Google Scholar]
  33. Mayer-Barber KD et al., 2014. Host-directed therapy of tuberculosis based on interleukin-1 and type I interferon crosstalk. Nature 511: 99–103.
     [Google Scholar]
  34. Yamada H, Mizumo S, Horai R, Iwakura Y, Sugawara I, 2000. Protective role of interleukin-1 in mycobacterial infection in IL-1 alpha/beta double-knockout mice. Lab Invest 80: 759–767.
     [Google Scholar]
  35. Ben-Sasson SZ et al., 2013. IL-1 enhances expansion, effector function, tissue localization, and memory response of antigen-specific CD8 T cells. J Exp Med 210: 491–502.
     [Google Scholar]
  36. Ushach I, Zlotnik A, 2016. Biological role of granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) on cells of the myeloid lineage. J Leukoc Biol 100: 481–489.
     [Google Scholar]
  37. Shi Y et al., 2006. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and T-cell responses: what we do and don’t know. Cell Res 16: 126–133.
     [Google Scholar]
  38. Rothchild AC et al., 2017. Role of granulocyte-macrophage colony-stimulating factor production by T cells during Mycobacterium tuberculosis infection. MBio 8: e01514-17.
     [Google Scholar]
  39. Kahnert A, Seiler P, Stein M, Bandermann S, Hahnke K, Mollenkopf H, Kaufmann SH, 2006. Alternative activation deprives macrophages of a coordinated defense program to Mycobacterium tuberculosis. Eur J Immunol 36: 631–647.
     [Google Scholar]
  40. Harris J, De Haro SA, Master SS, Keane J, Roberts EA, Delgado M, Deretic V, 2007. T helper 2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis. Immunity 27: 505–517.
     [Google Scholar]
  41. Redford PS, Murray PJ, O’Garra A, 2011. The role of IL-10 in immune regulation during M. tuberculosis infection. Mucosal Immunol 4: 261–270.
     [Google Scholar]
  42. Hirsch CS, Ellner JJ, Blinkhorn R, Toossi Z, 1997. In vitro restoration of T cell responses in tuberculosis and augmentation of monocyte effector function against Mycobacterium tuberculosis by natural inhibitors of transforming growth factor beta. Proc Natl Acad Sci USA 94: 3926–3393.
     [Google Scholar]
  43. Jafari C, Ernst M, Kalsdorf B, Greinert U, Diel R, Kirsten D, Marienfeld K, Lalvani A, Lange C, 2006. Rapid diagnosis of smear-negative tuberculosis by bronchoalveolar lavage enzyme-linked immunospot. Am J Respir Crit Care Med 174: 1048–1054.
     [Google Scholar]
  44. Wilkinson KA, Wilkinson RJ, Pathan A, Ewer K, Prakash M, Klenerman P, Maskell N, Davies R, Pasvol G, Lalvani A, 2005. Ex vivo characterization of early secretory antigenic target 6-specific T cells at sites of active disease in pleural tuberculosis. Clin Infect Dis 40: 184–187.
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.18-0834
Loading
Enhanced Mycobacterial Antigen–Induced Pro-Inflammatory Cytokine Production in Lymph Node Tuberculosis
The American Journal of Tropical Medicine and Hygiene 100, 1401 (2019); https://doi.org/10.4269/ajtmh.18-0834
/content/journals/10.4269/ajtmh.18-0834
/content/journals/10.4269/ajtmh.18-0834
Loading

Data & Media loading...

Supplemental figures

  • Supplementary File

Download
  • Received : 18 Oct 2018
  • Accepted : 26 Jan 2019
  • Published online : 15 Apr 2019

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error