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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24 Citations (Scopus)

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

ASJC Scopus subject areas

  • Immunology
  • Virology

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    Iannello, A., Samarani, S., Debbeche, O., Ahmad, R., Boulassel, M. R., Tremblay, C., Toma, E., Routy, J. P., & Ahmad, A. (2009). Potential role of interleukin-18 in the immunopathogenesis of AIDS: Involvement in fratricidal killing of NK cells. Journal of Virology, 83(12), 5999-6010. https://doi.org/10.1128/JVI.02350-08