Potential role of interleukin-18 in the immunopathogenesis of AIDS: Involvement in fratricidal killing of NK cells

Alexandre Iannello, Suzanne Samarani, Olfa Debbeche, Rasheed Ahmad, Mohamed Rachid Boulassel, Cécile Tremblay, Emil Toma, Jean Pierre Routy, Ali Ahmad

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Abstract

We had shown earlier that the concentrations of circulating interleukin-18 (IL-18) are increased significantly in human immunodeficiency virus (HIV)-infected persons compared to HIV-seronegative healthy subjects. In the present study, we investigated the consequences of these elevated levels of IL-18 on natural killer (NK) cells and the immunopathogenesis of AIDS. We show here an inverse correlation between IL-18 concentrations and absolute numbers of various subsets of NK cells in infected persons. Recombinant human IL-18 caused increased death of a human NK cell line, as well as of primary human NK cells in vitro. The IL-18-mediated cell death was dependent upon Fas-FasL interactions and tumor necrosis factor alpha. IL-18 induced the expression of FasL on NK cells, increased the transcription from the human FasL promoter, reduced the expression of Bcl-XL in NK cells, and increased their sensitivity to FasL-mediated cell death. These results suggest that increased IL-18 concentrations present in the circulation of HIV-infected persons contribute to the immunopathogenesis of AIDS by altering NK cell homeostasis.

Original languageEnglish
Pages (from-to)5999-6010
Number of pages12
JournalJournal of Virology
Volume83
Issue number12
DOIs
Publication statusPublished - Jun 2009

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interleukin-18
Interleukin-18
natural killer cells
Natural Killer Cells
Acquired Immunodeficiency Syndrome
Human immunodeficiency virus
HIV
cell death
Cell Death
tumor necrosis factor-alpha
homeostasis
Healthy Volunteers
Homeostasis
transcription (genetics)
Tumor Necrosis Factor-alpha
promoter regions
cell lines
death
Cell Line

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Potential role of interleukin-18 in the immunopathogenesis of AIDS : Involvement in fratricidal killing of NK cells. / Iannello, Alexandre; Samarani, Suzanne; Debbeche, Olfa; Ahmad, Rasheed; Boulassel, Mohamed Rachid; Tremblay, Cécile; Toma, Emil; Routy, Jean Pierre; Ahmad, Ali.

In: Journal of Virology, Vol. 83, No. 12, 06.2009, p. 5999-6010.

Research output: Contribution to journalArticle

Iannello, A, Samarani, S, Debbeche, O, Ahmad, R, Boulassel, MR, Tremblay, C, Toma, E, Routy, JP & Ahmad, A 2009, 'Potential role of interleukin-18 in the immunopathogenesis of AIDS: Involvement in fratricidal killing of NK cells', Journal of Virology, vol. 83, no. 12, pp. 5999-6010. https://doi.org/10.1128/JVI.02350-08
Iannello, Alexandre ; Samarani, Suzanne ; Debbeche, Olfa ; Ahmad, Rasheed ; Boulassel, Mohamed Rachid ; Tremblay, Cécile ; Toma, Emil ; Routy, Jean Pierre ; Ahmad, Ali. / Potential role of interleukin-18 in the immunopathogenesis of AIDS : Involvement in fratricidal killing of NK cells. In: Journal of Virology. 2009 ; Vol. 83, No. 12. pp. 5999-6010.
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