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

Research output: Contribution to journalArticle

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

Fingerprint

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.
@article{3bc4fc52231245029f40f94ad1c162b7,
title = "Potential role of interleukin-18 in the immunopathogenesis of AIDS: Involvement in fratricidal killing of NK cells",
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.",
author = "Alexandre Iannello and Suzanne Samarani and Olfa Debbeche and Rasheed Ahmad and Boulassel, {Mohamed Rachid} and C{\'e}cile Tremblay and Emil Toma and Routy, {Jean Pierre} and Ali Ahmad",
year = "2009",
month = "6",
doi = "10.1128/JVI.02350-08",
language = "English",
volume = "83",
pages = "5999--6010",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "12",

}

TY - JOUR

T1 - Potential role of interleukin-18 in the immunopathogenesis of AIDS

T2 - Involvement in fratricidal killing of NK cells

AU - Iannello, Alexandre

AU - Samarani, Suzanne

AU - Debbeche, Olfa

AU - Ahmad, Rasheed

AU - Boulassel, Mohamed Rachid

AU - Tremblay, Cécile

AU - Toma, Emil

AU - Routy, Jean Pierre

AU - Ahmad, Ali

PY - 2009/6

Y1 - 2009/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=66149120202&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=66149120202&partnerID=8YFLogxK

U2 - 10.1128/JVI.02350-08

DO - 10.1128/JVI.02350-08

M3 - Article

VL - 83

SP - 5999

EP - 6010

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 12

ER -