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
C2 - 19339355
AN - SCOPUS:66149120202
SN - 0022-538X
VL - 83
SP - 5999
EP - 6010
JO - Journal of Virology
JF - Journal of Virology
IS - 12
ER -
