1887

Abstract

Functional disruption of dendritic cells (DCs) is an important strategy for viral pathogens to evade host defences. Monocytotropic viruses such as classical swine fever virus (CSFV) could employ such a mechanism, since the virus can suppress immune responses and induce apoptosis without infecting lymphocytes. Here, CSFV was shown to infect and efficiently replicate in monocyte- and in bone marrow-derived DCs. Interestingly, the infected DCs displayed neither modulated MHC nor CD80/86 expression. Stimulation of DCs with IFN-/TNF- or polyinosinic–polycytidylic acid (pIC) induced phenotypic maturation with increased MHC and CD80/86 expression, both with mock-treated and infected DCs. In addition, the T cell stimulatory capacity of CSFV-infected DCs was maintained both in a polyclonal T cell stimulation and in specific antigen-presentation assays, requiring antigen uptake and processing. Interestingly, similar to macrophages, CSFV did not induce IFN- responses in these DCs and even suppressed pIC-induced IFN- induction. Other cytokines including interleukin (IL)-6, IL-10, IL-12 and TNF- were not modulated. Taken together, these results demonstrated that CSFV can replicate in DCs and control IFN type I responses, without interfering with the immune reactivity. These results are interesting considering that DC infection with RNA viruses usually results in DC activation.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19716-0
2004-06-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/85/6/vir851633.html?itemId=/content/journal/jgv/10.1099/vir.0.19716-0&mimeType=html&fmt=ahah

References

  1. Banchereau J., Briere F., Caux C., Davoust J., Lebecque S., Liu Y. J., Pulendran B., Palucka K. 2000; Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811 [CrossRef]
    [Google Scholar]
  2. Bhardwaj N., Friedman S. M., Cole B. C., Nisanian A. J. 1992; Dendritic cells are potent antigen-presenting cells for microbial superantigens. J Exp Med 175:267–273 [CrossRef]
    [Google Scholar]
  3. Carrasco C. P., Rigden R. C., Schaffner R. 7 other authors 2001; Porcine dendritic cells generated in vitro: morphological, phenotypic and functional properties. Immunology 104:175–184 [CrossRef]
    [Google Scholar]
  4. Cella M., Salio M., Sakakibara Y., Langen H., Julkunen I., Lanzavecchia A. 1999; Maturation, activation, and protection of dendritic cells induced by double-stranded RNA. J Exp Med 189:821–829 [CrossRef]
    [Google Scholar]
  5. Cheville N. F., Mengeling W. L. 1969; The pathogenesis of chronic hog cholera (swine fever). Histologic, immunofluorescent, and electron microscopic studies. Lab Invest 20:261–274
    [Google Scholar]
  6. Fugier-Vivier I., Servet-Delprat C., Rivailler P., Rissoan M. C., Liu Y. J., Rabourdin-Combe C. 1997; Measles virus suppresses cell-mediated immunity by interfering with the survival and functions of dendritic and T cells. J Exp Med 186:813–823 [CrossRef]
    [Google Scholar]
  7. Gardner J. P., Frolov I., Perri S. 13 other authors 2000; Infection of human dendritic cells by a Sindbis virus replicon vector is determined by a single amino acid substitution in the E2 glycoprotein. J Virol 74:11849–11857 [CrossRef]
    [Google Scholar]
  8. Glew E. J., Carr B. V., Brackenbury L. S., Hope J. C., Charleston B., Howard C. J. 2003; Differential effects of bovine viral diarrhoea virus on monocytes and dendritic cells. J Gen Virol 84:1771–1780 [CrossRef]
    [Google Scholar]
  9. Gomez-Villamandos J. C., Ruiz-Villamor E., Bautista M. J., Sanchez C. P., Sanchez-Cordon P. J., Salguero F. J., Jover A. 2001; Morphological and immunohistochemical changes in splenic macrophages of pigs infected with classical swine fever. J Comp Pathol 125:98–109 [CrossRef]
    [Google Scholar]
  10. Gomez-Villamandos J. C., Salguero F. J., Ruiz-Villamor E., Sanchez-Cordon P. J., Bautista M. J., Sierra M. A. 2003; Classical swine fever: pathology of bone marrow. Vet Pathol 40:157–163 [CrossRef]
    [Google Scholar]
  11. Greiser-Wilke I., Moennig V., Coulibaly C. O., Dahle J., Leder L., Liess B. 1990; Identification of conserved epitopes on a hog cholera virus protein. Arch Virol 111:213–225 [CrossRef]
    [Google Scholar]
  12. Greiser-Wilke I., Dittmar K. E., Liess B., Moennig V. 1992; Heterogeneous expression of the non-structural protein p80/p125 in cells infected with different pestiviruses. J Gen Virol 73:47–52 [CrossRef]
    [Google Scholar]
  13. Hammerberg C., Schurig G. G. 1986; Characterization of monoclonal antibodies directed against swine leukocytes. Vet Immunol Immunopathol 11:107–121 [CrossRef]
    [Google Scholar]
  14. Ho L. J., Wang J. J., Shaio M. F., Kao C. L., Chang D. M., Han S. W., Lai J. H. 2001; Infection of human dendritic cells by dengue virus causes cell maturation and cytokine production. J Immunol 166:1499–1506 [CrossRef]
    [Google Scholar]
  15. Inumaru S., Kokuho T., Denham S. 7 other authors 1998; Expression of biologically active recombinant porcine GM-CSF by baculovirus gene expression system. Immunol Cell Biol 76:195–201 [CrossRef]
    [Google Scholar]
  16. Johnston L. J., Halliday G. M., King N. J. 1996; Phenotypic changes in Langerhans cells after infection with arboviruses: a role in the immune response to epidermally acquired viral infection?. J Virol 70:4761–4766
    [Google Scholar]
  17. Klagge I. M., Schneider-Schaulies S. 1999; Virus interactions with dendritic cells. J Gen Virol 80:823–833
    [Google Scholar]
  18. Knoetig S. M., Summerfield A., Spagnuolo-Weaver M., McCullough K. C. 1999; Immunopathogenesis of classical swine fever: role of monocytic cells. Immunology 97:359–366 [CrossRef]
    [Google Scholar]
  19. Libraty D. H., Pichyangkul S., Ajariyakhajorn C., Endy T. P., Ennis F. A. 2001; Human dendritic cells are activated by dengue virus infection: enhancement by gamma interferon and implications for disease pathogenesis. J Virol 75:3501–3508 [CrossRef]
    [Google Scholar]
  20. Lopez C. B., Garcia-Sastre A., Williams B. R., Moran T. M. 2003; Type I interferon induction pathway, but not released interferon, participates in the maturation of dendritic cells induced by negative-strand RNA viruses. J Infect Dis 187:1126–1136 [CrossRef]
    [Google Scholar]
  21. MacPherson G. G., Liu L. M. 1999; Dendritic cells and Langerhans cells in the uptake of mucosal antigens. Curr Top Microbiol Immunol 236:33–53
    [Google Scholar]
  22. Mayer D., Thayer T. M., Hofmann M. A., Tratschin J. D. 2003; Establishment and characterisation of two cDNA-derived strains of classical swine fever virus, one highly virulent and one avirulent. Virus Res 98:105–116 [CrossRef]
    [Google Scholar]
  23. Moormann R. J., van Gennip H. G., Miedema G. K., Hulst M. M., van Rijn P. A. 1996; Infectious RNA transcribed from an engineered full-length cDNA template of the genome of a pestivirus. J Virol 70:763–770
    [Google Scholar]
  24. Pauly T., Konig M., Thiel H. J., Saalmuller A. 1998; Infection with classical swine fever virus: effects on phenotype and immune responsiveness of porcine T lymphocytes. J Gen Virol 79:31–40
    [Google Scholar]
  25. Pescovitz M. D., Lunney J. K., Sachs D. H. 1984; Preparation and characterization of monoclonal antibodies reactive with porcine PBL. J Immunol 133:368–375
    [Google Scholar]
  26. Pulendran B., Palucka K., Banchereau J. 2001; Sensing pathogens and tuning immune responses. Science 293:253–256 [CrossRef]
    [Google Scholar]
  27. Ressang A. A. 1973; Studies on the pathogenesis of hog cholera. II. Virus distribution in tissue and the morphology of the immune response. Zentbl Vetmed Reihe B 20:272–288
    [Google Scholar]
  28. Ruggli N., Tratschin J. D., Mittelholzer C., Hofmann M. A. 1996; Nucleotide sequence of classical swine fever virus strain Alfort/187 and transcription of infectious RNA from stably cloned full-length cDNA. J Virol 70:3478–3487
    [Google Scholar]
  29. Ruggli N., Tratschin J. D., Schweizer M., McCullough K. C., Hofmann M. A., Summerfield A. 2003; Classical swine fever virus interferes with cellular antiviral defense: evidence for a novel function of Npro . J Virol 77:7645–7654 [CrossRef]
    [Google Scholar]
  30. Sanchez-Cordon P. J., Romanini S., Salguero F. J., Nunez A., Bautista M. J., Jover A., Gomez-Villamos J. C. 2002; Apoptosis of thymocytes related to cytokine expression in experimental classical swine fever. J Comp Pathol 127:239–248 [CrossRef]
    [Google Scholar]
  31. Sanchez-Cordon P. J., Romanini S., Salguero F. J., Ruiz-Villamor E., Carrasco L., Gomez-Villamandos J. C. 2003; A histopathologic, immunohistochemical, and ultrastructural study of the intestine in pigs inoculated with classical swine fever virus. Vet Pathol 40:254–262 [CrossRef]
    [Google Scholar]
  32. Schweizer M., Peterhans E. 2001; Noncytopathic bovine viral diarrhea virus inhibits double-stranded RNA-induced apoptosis and interferon synthesis. J Virol 75:4692–4698 [CrossRef]
    [Google Scholar]
  33. Steinman R. M. 1991; The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 9:271–296 [CrossRef]
    [Google Scholar]
  34. Summerfield A., Hofmann M. A., McCullough K. C. 1998a; Low density blood granulocytic cells induced during classical swine fever are targets for virus infection. Vet Immunol Immunopathol 63:289–301 [CrossRef]
    [Google Scholar]
  35. Summerfield A., Knötig S. M., McCullough K. C. 1998b; Lymphocyte apoptosis during classical swine fever: implication of activation-induced cell death. J Virol 72:1853–1861
    [Google Scholar]
  36. Summerfield A., Knoetig S. M., Tschudin R., McCullough K. C. 2000; Pathogenesis of granulocytopenia and bone marrow atrophy during classical swine fever involves apoptosis and necrosis of uninfected cells. Virology 272:50–60 [CrossRef]
    [Google Scholar]
  37. Summerfield A., Zingle K., Inumaru S., McCullough K. C. 2001; Induction of apoptosis in bone marrow neutrophil-lineage cells by classical swine fever virus. J Gen Virol 82:1309–1318
    [Google Scholar]
  38. Summerfield A., Guzylack-Piriou L., Schaub A., Carrasco C. P., Tache V., Charley B. 2003; Porcine peripheral blood dendritic cells and natural interferon-producing cells. Immunology 110:440–449 [CrossRef]
    [Google Scholar]
  39. Susa M., König M., Saalmüller A., Reddehase M. J., Thiel H. J. 1992; Pathogenesis of classical swine fever: B-lymphocyte deficiency caused by hog cholera virus. J Virol 66:1171–1175
    [Google Scholar]
  40. Trautwein G. 1988; Pathology and pathogenesis of the disease. In Classical Swine Fever and Related Infections pp  27–54 Edited by Liess B. Boston: Martinus Nijhoff Publishing;
    [Google Scholar]
  41. Van Oirschot J. T., De Jong D., Huffels N. D. 1983; Effect of infections with swine fever virus on immune functions. II. Lymphocyte response to mitogens and enumeration of lymphocyte subpopulations. Vet Microbiol 8:81–95 [CrossRef]
    [Google Scholar]
  42. Vermes I., Haanen C., Steffens-Nakken H., Reutelingsperger C. 1995; A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods 184:39–51 [CrossRef]
    [Google Scholar]
  43. Von Niederhausern B., Bertoni G., Hertig C., Pfister H., Peterhans E., Pauli U. 1993; Cloning and expression in mammalian cells of porcine tumor necrosis factor alpha: examination of biological properties. Vet Immunol Immunopathol 38:57–74 [CrossRef]
    [Google Scholar]
  44. Wu S. J., Grouard-Vogel G., Sun W. 14 other authors 2000; Human skin Langerhans cells are targets of dengue virus infection. Nat Med 6:816–820 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19716-0
Loading
/content/journal/jgv/10.1099/vir.0.19716-0
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error