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Journal of General Virology header logo Journal of General Virology

Volume 85, Issue 8

Cytokine and contact-dependent activation of natural killer cells by influenza A or Sendai virus-infected macrophages No Access

Abstract

NK cells participate in innate immune responses by secreting gamma interferon (IFN-) and by destroying virus-infected cells. Here the interaction between influenza A or Sendai virus-infected macrophages and NK cells has been studied. A rapid, cell–cell contact-dependent production of IFN- from NK cells cultured with virus-infected macrophages was observed. Expression of the MHC class I-related chain B (MICB) gene, a ligand for NK cell-activating receptor NKG2D, was upregulated in virus-infected macrophages suggesting a role for MICB in the activation of the IFN- gene in NK cells. IL12R2, IL18R and T-bet mRNA synthesis was enhanced in NK cells cultured with virus-infected macrophages. Upregulation of these genes was dependent on macrophage-derived IFN-. In contrast to IL12R2, expression of WSX-1/TCCR, a receptor for IL27, was reduced in NK cells in response to virus-induced IFN-. In conclusion, these results show that virus-infected macrophages activate NK cells via cytokines and direct cellular interactions and further emphasize the role of IFN- in the activation of innate immunity.

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2004-08-01
2026-02-15

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References

  1. Afkarian M., Sedy J. R., Yang J., Jacobson N. G., Cereb N., Yang S. Y., Murphy T. L., Murphy K. M. 2002; T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells. Nat Immunol 3:549–557
     [Google Scholar]
  2. Bauer S., Groh V., Wu J., Steinle A., Phillips J. H., Lanier L. L., Spies T. 1999; Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 285:727–729 [CrossRef]
     [Google Scholar]
  3. Biron C. A. 1998; Role of early cytokines, including alpha and beta interferons (IFN- α / β ), in innate and adaptive immune responses to viral infections. Semin Immunol 10:383–390 [CrossRef]
     [Google Scholar]
  4. Biron C. A. 1999; Initial and innate responses to viral infections – pattern setting in immunity or disease. Curr Opin Microbiol 2:374–381 [CrossRef]
     [Google Scholar]
  5. Biron C. A., Byron K. S., Sullivan J. L. 1989; Severe herpesvirus infections in an adolescent without natural killer cells. N Engl J Med 320:1731–1735 [CrossRef]
     [Google Scholar]
  6. Biron C. A., Nguyen K. B., Pien G. C., Cousens L. P., Salazar-Mather T. P. 1999; Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 17:189–220 [CrossRef]
     [Google Scholar]
  7. Chen Q., Ghilardi N., Wang H., Baker T., Xie M. H., Gurney A., Grewal I. S., de Sauvage F. J. 2000; Development of Th1-type immune responses requires the type I cytokine receptor TCCR. Nature 407:916–920 [CrossRef]
     [Google Scholar]
  8. Colonna M. 1996; Natural killer cell receptors specific for MHC class I molecules. Curr Opin Immunol 8:101–107 [CrossRef]
     [Google Scholar]
  9. Cooper M. A., Fehniger T. A., Caligiuri M. A. 2001; The biology of human natural killer-cell subsets. Trends Immunol 22:633–640 [CrossRef]
     [Google Scholar]
  10. Cosman D., Mullberg J., Sutherland C. L., Chin W., Armitage R., Fanslow W., Kubin M., Chalupny N. J. 2001; ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity 14:123–133 [CrossRef]
     [Google Scholar]
  11. Cua D. J., Sherlock J., Chen Y. 13 other authors 2003; Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421:744–748 [CrossRef]
     [Google Scholar]
  12. Ferlazzo G., Tsang M. L., Moretta L., Melioli G., Steinman R. M., Munz C. 2002; Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. J Exp Med 195:343–351 [CrossRef]
     [Google Scholar]
  13. Garcia-Sastre A., Egorov A., Matassov D., Brandt S., Levy D. E., Durbin J. E., Palese P., Muster T. 1998; Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology 252:324–330 [CrossRef]
     [Google Scholar]
  14. Gong J. H., Maki G., Klingemann H. G. 1994; Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. Leukemia 8:652–658
     [Google Scholar]
  15. Hunter C. A., Timans J., Pisacane P. 7 other authors 1997; Comparison of the effects of interleukin-1 α , interleukin-1 β and interferon- γ -inducing factor on the production of interferon- γ by natural killer. Eur J Immunol 27:2787–2792 [CrossRef]
     [Google Scholar]
  16. Jinushi M., Takehara T., Kanto T. 7 other authors 2003; Critical role of MHC class I-related chain A and B expression on IFN- α -stimulated dendritic cells in NK cell activation: impairment in chronic hepatitis C virus infection. J Immunol 170:1249–1256 [CrossRef]
     [Google Scholar]
  17. Lighvani A. A., Frucht D. M., Jankovic D. 8 other authors 2001; T-bet is rapidly induced by interferon- γ in lymphoid and myeloid cells. Proc Natl Acad Sci U S A 98:15137–15142 [CrossRef]
     [Google Scholar]
  18. Long E. O. 1999; Regulation of immune responses through inhibitory receptors. Annu Rev Immunol 17:875–904 [CrossRef]
     [Google Scholar]
  19. Mandelboim O., Lieberman N., Lev M. 7 other authors 2001; Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells. Nature 409:1055–1060 [CrossRef]
     [Google Scholar]
  20. Matikainen S., Pirhonen J., Miettinen M., Lehtonen A., Govenius-Vintola C., Sareneva T., Julkunen I. 2000; Influenza A and Sendai viruses induce differential chemokine gene expression and transcription factor activation in human macrophages. Virology 276:138–147 [CrossRef]
     [Google Scholar]
  21. Matikainen S., Paananen A., Miettinen M., Kurimoto M., Timonen T., Julkunen I., Sareneva T. 2001; IFN- α and IL-18 synergistically enhance IFN- γ production in human NK cells: differential regulation of Stat4 activation and IFN- γ gene expression by IFN- α and IL-12. Eur J Immunol 31:2236–2245 [CrossRef]
     [Google Scholar]
  22. Micallef M. J., Ohtsuki T., Kohno K. 9 other authors 1996; Interferon- γ -inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon- γ production. Eur J Immunol 26:1647–1651 [CrossRef]
     [Google Scholar]
  23. Mogensen K. E., Pyhala L., Cantell K. 1975; Raising antibodies to human leukocyte interferon. Acta Pathol Microbiol Scand [B] 83:443–450
     [Google Scholar]
  24. Moretta A., Moretta L. 1997; HLA class I specific inhibitory receptors. Curr Opin Immunol 9:694–701 [CrossRef]
     [Google Scholar]
  25. Moretta A., Bottino C., Vitale M., Pende D., Biassoni R., Mingari M. C., Moretta L. 1996; Receptors for HLA class-I molecules in human natural killer cells. Annu Rev Immunol 14:619–648 [CrossRef]
     [Google Scholar]
  26. Moretta A., Bottino C., Vitale M., Pende D., Cantoni C., Mingari M. C., Biassoni R., Moretta L. 2001; Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. Annu Rev Immunol 19:197–223 [CrossRef]
     [Google Scholar]
  27. Nguyen K. B., Salazar-Mather T. P., Dalod M. Y., Van Deusen J. B., Wei X. Q., Liew F. Y., Caligiuri M. A., Durbin J. E., Biron C. A. 2002; Coordinated and distinct roles for IFN- αβ , IL-12 and IL-15 regulation of NK cell responses to viral infection. J Immunol 169:4279–4287 [CrossRef]
     [Google Scholar]
  28. Okamura H., Tsutsi H., Komatsu T. 7 other authors 1995; Cloning of a new cytokine that induces IFN- γ production by T cells. Nature 378:88–91 [CrossRef]
     [Google Scholar]
  29. Oppmann B., Lesley R., Blom B. 22 other authors 2000; Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity 13:715–725 [CrossRef]
     [Google Scholar]
  30. Orange J. S., Biron C. A. 1996; An absolute and restricted requirement for IL-12 in natural killer cell IFN- γ production and antiviral defense. Studies of natural killer and T cell responses in contrasting viral infections. J Immunol 156:1138–1142
     [Google Scholar]
  31. Parham C., Chirica M., Timans J. 19 other authors 2002; A receptor for the heterodimeric cytokine IL-23 is composed of IL-12R β 1 and a novel cytokine receptor subunit, IL-23R. J Immunol 168:5699–5708 [CrossRef]
     [Google Scholar]
  32. Pflanz S., Timans J. C., Cheung J. 18 other authors 2002; IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4+ T cells. Immunity 16:779–790 [CrossRef]
     [Google Scholar]
  33. Pirhonen J., Sareneva T., Kurimoto M., Julkunen I., Matikainen S. 1999; Virus infection activates IL-1 β and IL-18 production in human macrophages by a caspase-1-dependent pathway. J Immunol 162:7322–7329
     [Google Scholar]
  34. Pirhonen J., Sareneva T., Julkunen I., Matikainen S. 2001; Virus infection induces proteolytic processing of IL-18 in human macrophages via caspase-1 and caspase-3 activation. Eur J Immunol 31:726–733 [CrossRef]
     [Google Scholar]
  35. Pirhonen J., Matikainen S., Julkunen I. 2002; Regulation of virus-induced IL-12 and IL-23 expression in human macrophages. J Immunol 169:5673–5678 [CrossRef]
     [Google Scholar]
  36. Ravetch J. V., Lanier L. L. 2000; Immune inhibitory receptors. Science 290:84–89 [CrossRef]
     [Google Scholar]
  37. Rogge L., Barberis-Maino L., Biffi M., Passini N., Presky D. H., Gubler U., Sinigaglia F. 1997; Selective expression of an interleukin-12 receptor component by human T helper 1 cells. J Exp Med 185:825–831 [CrossRef]
     [Google Scholar]
  38. Sareneva T., Pirhonen J., Cantell K., Kalkkinen N., Julkunen I. 1994; Role of N -glycosylation in the synthesis, dimerization and secretion of human interferon- γ . Biochem J 303:831–840
     [Google Scholar]
  39. Sareneva T., Matikainen S., Kurimoto M., Julkunen I. 1998; Influenza A virus-induced IFN- α / β and IL-18 synergistically enhance IFN- γ gene expression in human T cells. J Immunol 160:6032–6038
     [Google Scholar]
  40. Sareneva T., Julkunen I., Matikainen S. 2000; IFN- α and IL-12 induce IL-18 receptor gene expression in human NK and T cells. J Immunol 165:1933–1938 [CrossRef]
     [Google Scholar]
  41. Spaggiari G. M., Carosio R., Pende D., Marcenaro S., Rivera P., Zocchi M. R., Moretta L., Poggi A. 2001; NK cell-mediated lysis of autologous antigen-presenting cells is triggered by the engagement of the phosphatidylinositol 3-kinase upon ligation of the natural cytotoxicity receptors NKp30 and NKp46. Eur J Immunol 31:1656–1665 [CrossRef]
     [Google Scholar]
  42. Strengell M., Sareneva T., Foster D., Julkunen I., Matikainen S. 2002; IL-21 up-regulates the expression of genes associated with innate immunity and Th1 response. J Immunol 169:3600–3605 [CrossRef]
     [Google Scholar]
  43. Sutherland C. L., Chalupny N. J., Schooley K., VandenBos T., Kubin M., Cosman D. 2002; UL16-binding proteins, novel MHC class I-related proteins, bind to NKG2D and activate multiple signaling pathways in primary NK cells. J Immunol 168:671–679 [CrossRef]
     [Google Scholar]
  44. Szabo S. J., Kim S. T., Costa G. L., Zhang X., Fathman C. G., Glimcher L. H. 2000; A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100:655–669 [CrossRef]
     [Google Scholar]
  45. Szabo S. J., Sullivan B. M., Stemmann C., Satoskar A. R., Sleckman B. P., Glimcher L. H. 2002; Distinct effects of T-bet in TH1 lineage commitment and IFN- γ production in CD4 and CD8 T cells. Science 295:338–342 [CrossRef]
     [Google Scholar]
  46. Tortorella D., Gewurz B. E., Furman M. H., Schust D. J., Ploegh H. L. 2000; Viral subversion of the immune system. Annu Rev Immunol 18:861–926 [CrossRef]
     [Google Scholar]
  47. Trinchieri G. 1989; Biology of natural killer cells. Adv Immunol 47:187–376
     [Google Scholar]
  48. Trinchieri G. 1997; Cytokines acting on or secreted by macrophages during intracellular infection (IL-10, IL-12, IFN- γ ). Curr Opin Immunol 9:17–23 [CrossRef]
     [Google Scholar]
  49. Trinchieri G. 2003; Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 3:133–146 [CrossRef]
     [Google Scholar]
  50. Wang X., Li M., Zheng H., Muster T., Palese P., Beg A. A., Garcia-Sastre A. 2000; Influenza A virus NS1 protein prevents activation of NF- κ B and induction of α / β interferon. J Virol 74:11566–11573 [CrossRef]
     [Google Scholar]
  51. Wu J., Song Y., Bakker A. B., Bauer S., Spies T., Lanier L. L., Phillips J. H. 1999; An activating immunoreceptor complex formed by NKG2D and DAP10. Science 285:730–732 [CrossRef]
     [Google Scholar]
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Cytokine and contact-dependent activation of natural killer cells by influenza A or Sendai virus-infected macrophages
J. Gen. Virol. 85, 2357 (2004); https://doi.org/10.1099/vir.0.80105-0
/content/journal/jgv/10.1099/vir.0.80105-0
/content/journal/jgv/10.1099/vir.0.80105-0
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