Role of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand in Immune Response to Influenza Virus Infection in Mice

ABSTRACT 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.

[1]  P. Secchiero,et al.  Human herpesvirus 7 induces the functional up-regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) coupled to TRAIL-R1 down-modulation in CD4(+) T cells. , 2001, Blood.

[2]  P. Hersey,et al.  Tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of human melanoma is regulated by smac/DIABLO release from mitochondria. , 2001, Cancer research.

[3]  T. McDonnell,et al.  TRAIL (APO-2L) induces apoptosis in human prostate cancer cells that is inhibitable by Bcl-2 , 2001, Oncogene.

[4]  Xuetao Cao,et al.  The Involvement of TNF-α-Related Apoptosis-Inducing Ligand in the Enhanced Cytotoxicity of IFN-β-Stimulated Human Dendritic Cells to Tumor Cells1 , 2001, The Journal of Immunology.

[5]  K. Tyler,et al.  Reovirus-Induced Apoptosis Is Mediated by TRAIL , 2000, Journal of Virology.

[6]  M. Kaplan,et al.  TRAIL (Apo2 Ligand) and TWEAK (Apo3 Ligand) Mediate CD4+ T Cell Killing of Antigen-Presenting Macrophages1 , 2000, The Journal of Immunology.

[7]  Michael T. Fisher,et al.  Molecular determinants of response to TRAIL in killing of normal and cancer cells. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[8]  Y. Nagashima,et al.  Dendritic cells are associated with augmentation of antigen sensitization by influenza A virus infection in mice , 2000, European journal of immunology.

[9]  K. Schooley,et al.  Human Dendritic Cells Mediate Cellular Apoptosis via Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (Trail) , 1999, The Journal of experimental medicine.

[10]  H. Okamura,et al.  Expression and function of TNF-related apoptosis-inducing ligand on murine activated NK cells. , 1999, Journal of immunology.

[11]  J. Peschon,et al.  IFN-gamma mediates a novel antiviral activity through dynamic modulation of TRAIL and TRAIL receptor expression. , 1999, Journal of immunology.

[12]  J. Puck,et al.  Inherited Human Caspase 10 Mutations Underlie Defective Lymphocyte and Dendritic Cell Apoptosis in Autoimmune Lymphoproliferative Syndrome Type II , 1999, Cell.

[13]  E. Alnemri,et al.  Molecular cloning and functional analysis of the mouse homologue of the KILLER/DR5 tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor. , 1999, Cancer research.

[14]  K. Okumura,et al.  Type I Interferons (IFNs) Regulate Tumor Necrosis Factor–related Apoptosis-inducing Ligand (TRAIL) Expression on Human T Cells: A Novel Mechanism for the Antitumor Effects of  Type I IFNs , 1999, The Journal of experimental medicine.

[15]  C. Maliszewski,et al.  Monocyte-mediated Tumoricidal Activity via the Tumor Necrosis Factor–related Cytokine, TRAIL , 1999, The Journal of experimental medicine.

[16]  C. Smith,et al.  Functional analysis of TRAIL receptors using monoclonal antibodies. , 1999, Journal of immunology.

[17]  C. Rauch,et al.  Tumoricidal activity of tumor necrosis factor–related apoptosis–inducing ligand in vivo , 1999, Nature Medicine.

[18]  T. Griffith,et al.  Intracellular regulation of TRAIL-induced apoptosis in human melanoma cells. , 1998, Journal of immunology.

[19]  M. Martínez-Lorenzo,et al.  Involvement of APO2 ligand/TRAIL in activation‐induced death of Jurkat and human peripheral blood T cells , 1998, European journal of immunology.

[20]  V. Dixit,et al.  Death receptors: signaling and modulation. , 1998, Science.

[21]  P. Krammer,et al.  Surface expression of TRAIL/Apo‐2 ligand in activated mouse T and B cells , 1998, European journal of immunology.

[22]  C. Smith,et al.  The novel receptor TRAIL-R4 induces NF-kappaB and protects against TRAIL-mediated apoptosis, yet retains an incomplete death domain. , 1997, Immunity.

[23]  P. Doherty,et al.  CD8+ T cells clear influenza virus by perforin or Fas-dependent processes. , 1997, Journal of immunology.

[24]  G. Karupiah,et al.  Cytokines and immunity to viral infections , 1997, Immunological reviews.

[25]  R. Gentz,et al.  An antagonist decoy receptor and a death domain-containing receptor for TRAIL. , 1997, Science.

[26]  W I Wood,et al.  Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors. , 1997, Science.

[27]  T. Gura.  How TRAIL Kills Cancer Cells, But Not Normal Cells , 1997, Science.

[28]  A. Morris,et al.  Cytokine research: the interferon paradigm. , 1997, Journal of clinical pathology.

[29]  I. Gresser,et al.  Wherefore interferon? , 1997, Journal of leukocyte biology.

[30]  Arul M. Chinnaiyan,et al.  The Receptor for the Cytotoxic Ligand TRAIL , 1997, Science.

[31]  S. Nagata,et al.  Apoptosis by Death Factor , 1997, Cell.

[32]  S. Marsters,et al.  Induction of Apoptosis by Apo-2 Ligand, a New Member of the Tumor Necrosis Factor Cytokine Family* , 1996, The Journal of Biological Chemistry.

[33]  C A Smith,et al.  Identification and characterization of a new member of the TNF family that induces apoptosis. , 1995, Immunity.

[34]  P. Erb,et al.  Mechanism and Biological Significance of CD4‐mediated Cytotoxicity , 1995, Immunological reviews.

[35]  S. Hanabuchi,et al.  Fas‐mediated Cytotoxicity ‐ A New Immunoregulatory and Pathogenic Function of Thl CD4+ T Cells , 1995, Immunological reviews.

[36]  J. Tschopp,et al.  Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways , 1994, Nature.

[37]  K. Okumura,et al.  Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes. , 1994, Immunity.

[38]  H Hengartner,et al.  Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. , 1994, Science.

[39]  K. Frei,et al.  A kinetic study of immune mediators in the lungs of mice infected with influenza A virus. , 1992, Journal of immunology.

[40]  X. Cao,et al.  The involvement of TNF-alpha-related apoptosis-inducing ligand in the enhanced cytotoxicity of IFN-beta-stimulated human dendritic cells to tumor cells. , 2001, Journal of immunology.

[41]  M. Smyth,et al.  Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells , 2001, Nature Medicine.

[42]  C. Le Page,et al.  Interferon activation and innate immunity. , 2000, Reviews in immunogenetics.

[43]  R. Zinkernagel,et al.  Molecular mechanisms of lymphocyte-mediated cytotoxicity and their role in immunological protection and pathogenesis in vivo. , 1996, Annual review of immunology.