Plasma granulysin levels and cellular interferon-γ production correlate with curative host responses in tuberculosis, while plasma interferon-γ levels correlate with tuberculosis disease activity in adults

E. Sahiratmadja, B. Alisjahbana, S. Buccheri, D. Di Liberto, T. de Boer, I. Adnan, R. van Crevel, M. R. Klein, K. E. van Meijgaarden, R. H H Nelwan, E. van de Vosse, F. Dieli, T. H M Ottenhoff

Research output: Contribution to journalArticle

Abstract

Granulysin is a recently identified cytolytic protein which is expressed by human cytotoxic T-lymphocytes and natural killer (NK)-cells, and has broad antimicrobial and tumoricidal activity. Circulating granulysin levels are associated with T- and NK-cell activity, and may thus reflect protection-associated cellular immune responses. In a case-control study in Indonesia, a highly tuberculosis (TB)-endemic country, we therefore determined plasma granulysin levels in adults with active pulmonary TB before, during, and after TB treatment, both in mild/moderate-TB and advanced-TB patients, and compared these to healthy neighbourhood controls. Adults with active pulmonary TB had significantly lower plasma granulysin levels compared to controls. After 2 months of anti-TB therapy, levels in TB patients had significantly increased, reaching values similar to those in controls. Plasma granulysin levels further increased after completion of TB therapy, being significantly higher than those in controls. Plasma granulysin levels correlated inversely with TB disease activity but not with TB disease severity. In contrast, plasma interferon-γ (IFN-γ) levels were significantly higher in active TB cases than in controls, normalised during treatment and correlated with both TB disease activity and TB disease severity. At the cellular level, granulysin and IFN-γ expression both correlated inversely with disease activity. Interestingly, granulysin was predominantly expressed by IFN-γ negative T-cells, suggesting that the cellular sources of IFN-γ and granulysin in TB are partly non-overlapping. The observation that plasma granulysin levels and cellular IFN-γ production correlate with curative host responses in pulmonary tuberculosis points to a potentially important role of granulysin, next to IFN-γ, in host defence against M. tuberculosis.

Original languageEnglish
Pages (from-to)312-321
Number of pages10
JournalTuberculosis
Volume87
Issue number4
DOIs
Publication statusPublished - Jul 2007

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interferons
tuberculosis
Interferons
Tuberculosis
Pulmonary Tuberculosis
lungs
natural killer cells
disease severity
Natural Killer T-Cells
Indonesia
Cytotoxic T-Lymphocytes
Therapeutics
therapeutics
cytotoxic T-lymphocytes
Cellular Immunity
Natural Killer Cells
Case-Control Studies
case-control studies
cell-mediated immunity

Keywords

  • Cellular granulysin
  • Cellular IFN-γ
  • Disease severity
  • Plasma granulysin
  • Plasma IFN-γ
  • Tuberculosis

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Microbiology
  • Immunology and Allergy
  • Infectious Diseases
  • veterinary(all)

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Plasma granulysin levels and cellular interferon-γ production correlate with curative host responses in tuberculosis, while plasma interferon-γ levels correlate with tuberculosis disease activity in adults. / Sahiratmadja, E.; Alisjahbana, B.; Buccheri, S.; Di Liberto, D.; de Boer, T.; Adnan, I.; van Crevel, R.; Klein, M. R.; van Meijgaarden, K. E.; Nelwan, R. H H; van de Vosse, E.; Dieli, F.; Ottenhoff, T. H M.

In: Tuberculosis, Vol. 87, No. 4, 07.2007, p. 312-321.

Research output: Contribution to journalArticle

Sahiratmadja, E, Alisjahbana, B, Buccheri, S, Di Liberto, D, de Boer, T, Adnan, I, van Crevel, R, Klein, MR, van Meijgaarden, KE, Nelwan, RHH, van de Vosse, E, Dieli, F & Ottenhoff, THM 2007, 'Plasma granulysin levels and cellular interferon-γ production correlate with curative host responses in tuberculosis, while plasma interferon-γ levels correlate with tuberculosis disease activity in adults', Tuberculosis, vol. 87, no. 4, pp. 312-321. https://doi.org/10.1016/j.tube.2007.01.002
Sahiratmadja, E. ; Alisjahbana, B. ; Buccheri, S. ; Di Liberto, D. ; de Boer, T. ; Adnan, I. ; van Crevel, R. ; Klein, M. R. ; van Meijgaarden, K. E. ; Nelwan, R. H H ; van de Vosse, E. ; Dieli, F. ; Ottenhoff, T. H M. / Plasma granulysin levels and cellular interferon-γ production correlate with curative host responses in tuberculosis, while plasma interferon-γ levels correlate with tuberculosis disease activity in adults. In: Tuberculosis. 2007 ; Vol. 87, No. 4. pp. 312-321.
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abstract = "Granulysin is a recently identified cytolytic protein which is expressed by human cytotoxic T-lymphocytes and natural killer (NK)-cells, and has broad antimicrobial and tumoricidal activity. Circulating granulysin levels are associated with T- and NK-cell activity, and may thus reflect protection-associated cellular immune responses. In a case-control study in Indonesia, a highly tuberculosis (TB)-endemic country, we therefore determined plasma granulysin levels in adults with active pulmonary TB before, during, and after TB treatment, both in mild/moderate-TB and advanced-TB patients, and compared these to healthy neighbourhood controls. Adults with active pulmonary TB had significantly lower plasma granulysin levels compared to controls. After 2 months of anti-TB therapy, levels in TB patients had significantly increased, reaching values similar to those in controls. Plasma granulysin levels further increased after completion of TB therapy, being significantly higher than those in controls. Plasma granulysin levels correlated inversely with TB disease activity but not with TB disease severity. In contrast, plasma interferon-γ (IFN-γ) levels were significantly higher in active TB cases than in controls, normalised during treatment and correlated with both TB disease activity and TB disease severity. At the cellular level, granulysin and IFN-γ expression both correlated inversely with disease activity. Interestingly, granulysin was predominantly expressed by IFN-γ negative T-cells, suggesting that the cellular sources of IFN-γ and granulysin in TB are partly non-overlapping. The observation that plasma granulysin levels and cellular IFN-γ production correlate with curative host responses in pulmonary tuberculosis points to a potentially important role of granulysin, next to IFN-γ, in host defence against M. tuberculosis.",
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