Role of tumor necrosis factor-related apoptosis-inducing ligand in immune response to influenza virus infection in mice.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis of various tumor cells but not normal cells. However, various cytokines and virus infection differentially regulate TRAIL and TRAIL receptor expression. It has been demonstrated that virus infection changes the pattern of human TRAIL-receptor expression on normal cells, which were resistant to TRAIL-mediated apoptosis, and makes them susceptible to TRAIL-mediated apoptosis. Since previous studies on the function of TRAIL have been performed mainly in vitro, its physiological role in the immune response to virus infection remains unknown. In the present study, we investigated the expression of TRAIL in the lungs of influenza virus-infected mice and the function of TRAIL in the immune response to infection. Influenza virus infection increased TRAIL mRNA expression in the lung. TRAIL protein expression was induced on NK cells in the lung 4 days after infection. At 7 days after infection, TRAIL protein expression was also detected on CD4(+) and CD8(+) T cells. However, NK cells and T cells in the lungs of uninfected mice did not express a detectable level of TRAIL on their cell surfaces. DR5, which is a mouse TRAIL receptor, was also induced to express after virus infection. Expression of both TRAIL and DR5 mRNAs was reduced to normal level at 6 weeks after virus infection. Administration of anti-TRAIL monoclonal antibody, which blocks TRAIL without killing TRAIL-expressing cells, to mice during influenza virus infection significantly delayed virus clearance in the lung. These results suggest that TRAIL plays an important role in the immune response to virus infection.
Ishikawa
Eri
E
Department of Immunology, Yokohama City University School of Medicine, Fukuura 3-9, Kanazawa-ku, Yokohama 236-0004, Japan.
Nakazawa
Masatoshi
M
Yoshinari
Masahiro
M
Minami
Mutsuhiko
M
D000818:Animals; D000911:Antibodies, Monoclonal; D051017:Apoptosis Regulatory Proteins; D006801:Humans; D009980:Influenza A virus / Q000276:immunology / Q000472:pathogenicity*; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D007694:Killer Cells, Natural / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; C505640:Tnfrsf10b protein, mouse; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha