1887

Abstract

Fifteen 8-week-old conventional pigs were selected from a farm where pigs were suffering from postweaning multisystemic wasting syndrome (PMWS). Ten of the animals were diseased pigs showing typical signs of PMWS (wasting and respiratory disorders) and positive for infection with porcine circovirus type 2 (PCV2), and the other five animals selected as controls were pen-mate, apparently healthy pigs. Blood samples and lymphoid tissues were taken from each animal for haematological, serological and histopathological studies. Also, cytokine mRNA expression of IL-1, IL-2, IL-4, IL-8, IL-10, IL-12p40 and IFN- from inguinal and bronchial lymph nodes, tonsils, spleen and thymus was determined by semi-quantitative RT-PCR. Pigs suffering from PMWS showed severe alterations of haematological parameters such as anaemia, lymphopenia with decrease of CD8 and IgM cells, monocytosis and neutrophilia. Also, extensive lymphocyte depletion and altered cytokine mRNA expression patterns were seen in most of the examined lymphoid organs. Those cytokine mRNA alterations were characterized by an overexpression of IL-10 mRNA in thymus and IFN- mRNA in tonsils, and by decreases in the mRNA expression of several cytokines as IL-2 and IL-12p40 in the spleen, IL-4 in tonsils, and IFN-, IL-10, IL-12p40 and IL-4 in inguinal lymph nodes. Also, the IL-10 mRNA overexpression was histologically associated with the thymic depletion and atrophy observed in PMWS pigs. In conclusion, the cytokine mRNA imbalance, specially the increased mRNA levels of IL-10 in the thymus, jointly with the histopathological and haematological disorders, are highly indicative of a T-cell immunosuppression, enhancing the notion that the immune system of PMWS-affected pigs is severely impaired.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19124-0
2003-08-01
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/8/vir842117.html?itemId=/content/journal/jgv/10.1099/vir.0.19124-0&mimeType=html&fmt=ahah

References

  1. Adair B. M. 2000; Immunopathogenesis of chicken anemia virus infection. Dev Comp Immunol 24:247–255
    [Google Scholar]
  2. Adair B. M., McNeilly F., McConnell C. D. G., Todd D., Nelson R. T., McNulty M. S. 1991; Effects of chicken anemia agent on lymphokyne production and lymphocyte transformation in experimentally infected chickens. Avian Dis 35:783–792
    [Google Scholar]
  3. Allan G. M., Kennedy S. 1999; Experimental reproduction of severe wasting disease by co-infection of pigs with porcine circovirus and porcine parvovirus. J Comp Pathol 121:1–11
    [Google Scholar]
  4. Allan G. M., McNeilly F., Kennedy S., Daft B., Clarke E. G., Ellis J. A., Haines D. M., Meehan B. M., Adair B. M. 1998; Isolation of porcine circovirus-like viruses from pigs with a wasting disease in the USA and Europe. J Vet Diagn Invest 10:3–10
    [Google Scholar]
  5. Allan G. M., McNeilly F., Ellis J., Krakowka S., Meehan B., McNair I., Walker I., Kennedy S. 2000; Experimental infection of colostrum deprived piglets with porcine circovirus 2 (PCV2) and porcine reproductive and respiratory syndrome virus (PRRS) potentiates PCV2 replication. Arch Virol 145:2421–2429
    [Google Scholar]
  6. Balasch M., Segalés J., Rosell C., Domingo M., Mankertz A., Urniza A., Plana-Durán J. 1999; Experimental inoculation of conventional pigs with tissue homogenates from pigs with postweaning multisystemic wasting syndrome. J Comp Pathol 121:139–148
    [Google Scholar]
  7. Bolin S. R., Stoffregen W. C., Nayar G. P. S., Hamel A. L. 2001; Postweaning multisystemic wasting syndrome induced after experimental inoculation of cesarean-derived, colostrum-deprived piglets with type 2 porcine circovirus. J Vet Diagn Invest 13:185–194
    [Google Scholar]
  8. Carrasco L., Segalés J., Bautista M. J., Gómez-Villamandos J. C., Rosell C., Ruiz Villamor E., Sierra M. A. 2000; Intestinal chlamydial infection concurrent with postweaning wasting syndrome in pigs. Vet Rec 146:21–23
    [Google Scholar]
  9. Choi C., Chae C., Clark E. G. 2000; Porcine postweaning multisystemic wasting syndrome in Korean pig: detection of porcine circovirus 2 infection by immunohistochemistry and polymerase chain reaction. J Vet Diagn Invest 12:151–153
    [Google Scholar]
  10. Clark E. G. 1997; Post-weaning multisystemic wasting syndrome. Proc Am Assoc Swine Practit 28:499–501
    [Google Scholar]
  11. Darwich L., Segalés J., Domingo M., Mateu E. 2002; Changes in the CD4+, CD8+, CD4/CD8 double positive cells and IgM+ cell subsets in peripheral blood mononuclear cells from postweaning multisystemic wasting syndrome affected pigs and age matched uninfected wasted and healthy pigs, correlates with lesions and porcine circovirus type 2 load in lymphoid tissues. Clin Diagn Lab Immunol 9:236–242
    [Google Scholar]
  12. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. 1991; Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 174:1209–1220
    [Google Scholar]
  13. Dozois C. M., Oswald E., Gautier N., Serthelon J. P., Fairbrother J. M., Oswald I. P. 1997; A reverse transcription-polymerase chain reaction method to analyze porcine cytokine gene expression. Vet Immunol Immunopathol 58:287–300
    [Google Scholar]
  14. Ellis J., Hassard L., Clark E. 9 other authors 1998; Isolation of circovirus from lesions of pigs with postweaning multisystemic wasting syndrome. Can Vet J 39:44–51
    [Google Scholar]
  15. Ellis J. A., Bratanich A., Clark E. G. 10 other authors 2000; Coinfection by porcine circoviruses and porcine parvovirus in pigs with naturally acquired postweaning multisystemic wasting syndrome. J Vet Diagn Invest 12:21–27
    [Google Scholar]
  16. Fournout S., Dozois M., Odin M. 9 other authors 2000; Lack of a role of cytotoxic necrotizing factor 1 toxin from Escherichia coli in bacterial pathogenicity and host cytokine response in infected germfree piglets. Infect Immun 68:839–847
    [Google Scholar]
  17. Hamel A. L., Lin L. L., Nayar G. P. S. 1998; Nucleotide sequence of porcine circovirus associated with postweaning multisystemic wasting syndrome in pigs. J Virol 72:5262–5267
    [Google Scholar]
  18. Harding J. C. 1997; Post-weaning multisystemic wasting syndrome (PMWS): preliminary epidemiology and clinical presentation. Proc American Association of Swine Practitioners 28:503
    [Google Scholar]
  19. Harms P. A., Sorden S. D., Halbur P. G., Bolin S. R., Lager K. M., Morozov I., Paul P. S. 2001; Experimental reproduction of severe disease in CD/CD pigs concurrently infected with type 2 porcine circovirus and porcine reproductive and respiratory syndrome virus. Vet Pathol 38:528–539
    [Google Scholar]
  20. Jain N. C. 1993; Examination of the blood and bone marrow. In Essentials of Veterinary Hematology pp  7–23 Edited by Mundorff G. H. USA: Lea & Febiger;
    [Google Scholar]
  21. Kennedy S., Moffett D., McNeilly F., Meehan B., Ellis J., Krakowka S., Allan G. M. 2000; Reproduction of lesions of postweaning multisystemic wasting syndrome by infection of conventional pigs with porcine circovirus type 2 alone or in combination with porcine parvovirus. J Comp Pathol 122:9–24
    [Google Scholar]
  22. Kim J., Choi C., Chae C. 2003; Pathogenesis of postweaning multisystemic wasting syndrome reproduced by co-infection with Korean isolates of porcine circovirus 2 and porcine parvovirus. J Comp Pathol 128:52–59
    [Google Scholar]
  23. Kiupel M., Stevenson G. W., Mittal S. K., Clark E. G., Haines D. M. 1998; Circovirus-like viral associated disease in weaned pigs in Indiana. Vet Pathol 35:303–307
    [Google Scholar]
  24. Kiupel M., Stevenson G. W., Kanitz C. L., Anothayanontha L., Latimer K. S., Mittal S. K. 1999; Cellular localization of porcine circovirus in postweaning pigs with chronic wasting disease. Eur J Vet Pathol 5:77–82
    [Google Scholar]
  25. Kovalev G., Duus K., Wang L., Lee R., Bonyhadi M., Ho D., McCune J. M., Kaneshima H., Su L. 1999; Induction of MHC class I expression on immature thymocytes in HIV-1 infected SCID-hu Thy/Liv mice: evidence of indirect mechanisms. J Immunol 162:7555–7562
    [Google Scholar]
  26. Krakowka S., Ellis J. A., Meehan B., Kennedy S., McNeilly F., Allan G. 2000; Viral wasting syndrome of swine: experimental reproduction of PMWS in gnotobiotics swine by co-infection with porcine circovirus-2 (PCV-2) and porcine parvovirus (PPV. Vet Pathol 37:254–263
    [Google Scholar]
  27. Krakowka S., Ellis J. A., McNeilly F., Ringler S., Rings D. M., Allan G. 2001; Activation of the immune system is the pivotal event in the production of wasting disease in pigs infected with porcine circovirus -2 (PCV-2). Vet Pathol 38:31–42
    [Google Scholar]
  28. Ladekjaer-Mikkelsen A.-S., Nielsen J., Stadejek T., Storgaard T., Krakowka S., Ellis J., McNeilly F., Allan G., Botner A. 2002; Reproduction of postweaning multisystemic wasting syndrome (PMWS) in immunostimulated and non-immunostimulated 3-week-old piglets experimentally infected with porcine circovirus type 2 (PCV2). Vet Microbiol 89:97–114
    [Google Scholar]
  29. Leman A. D. 1986; Cardiovascular system, haematology, and clinical chemistry. In Diseases of Swine , 6th edn. Edited by Leman A. D. Ames: Iowa State University Press;
    [Google Scholar]
  30. Levy Y., Brouet J. C. 1994; Interleukin-10 prevents spontaneous death of germinal center B-cells by induction of the bcl-2 protein. J Clin Investig 93:424–428
    [Google Scholar]
  31. Madec F., Eveno E., Morvan P. 9 other authors 2000; Post-weaning multisystemic wasting syndrome (PMWS) in pigs in France: clinical observations from follow-up studies on affected farms. Livest Prod Sci 63:223–233
    [Google Scholar]
  32. Marin D. E., Taranu I., Bunaciu R. P. 8 other authors 2002; Changes in performance, blood parameters, humoral and cellular immune responses in weaning piglets exposed to low doses of aflatoxin. J Anim Sci 80:1250–1257
    [Google Scholar]
  33. Meehan B. M., McNeilly F., Todd D. 7 other authors 1998; Characterization of novel circovirus DNAs associated with wasting syndromes in pigs. J Gen Virol 79:2171–2179
    [Google Scholar]
  34. Moore K. W., de Waal Malefyt R., Coffman R. L., O'Garra A. 2001; Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765
    [Google Scholar]
  35. Muraille E., Leo O. 1998; Revisiting the Th1/Th2 paradigm. Scand J Immunol 47:1–9
    [Google Scholar]
  36. Onuki A., Abe K., Togashi K., Kawashima K., Taneichi A., Tsunemitsu H. 1999; Detection of porcine circovirus from lesions of a pig with wasting disease in Japan. J Vet Med Sci 61:1119–1123
    [Google Scholar]
  37. Pié S., Matsiota-Bernard P., Truffa-Bachi P., Nauciel C. 1996; Gamma interferon and interleukin-10 gene expression in innately susceptible and resistant mice during the early phase of Salmonella typhimurium infection. Infect Immun 64:849–854
    [Google Scholar]
  38. Quintana J., Segalés J., Rosell C. 8 other authors 2001; Clinical and pathological observations on pigs with postweaning multisystemic wasting syndrome. Vet Rec 149:357–361
    [Google Scholar]
  39. Rodríguez-Arrioja G. M., Segalés J., Balasch M., Rosell C., Quintana J., Folch J. M., Plana-Durán J., Mankertz A., Domingo M. 2000; Serum antibodies to porcine circovirus type 1 and type 2 in pigs with and without PMWS. Vet Rec 146:762–764
    [Google Scholar]
  40. Rosell C., Segalés J., Plana-Durán J. 7 other authors 1999; Pathological, immunohistochemical and in-situ hybridisation studies of natural cases of postweaning multisystemic wasting syndrome (PMWS) in pigs. J Comp Pathol 120:59–78
    [Google Scholar]
  41. Rosell C., Segalés J., Domingo M. 2000; Hepatitis and staging of hepatic damage in pigs naturally infected with porcine circovirus type 2. Vet Pathol 37:687–692
    [Google Scholar]
  42. Rouleau M., Cottrez F., Bigler M., Antonenko S., Carballido J. M., Zlotnik A., Roncarolo M. G., Groux H. 1999; IL-10 transgenic mice present a defect in T cell development reminiscent to SCID patients. J Immunol 163:1420–1427
    [Google Scholar]
  43. Rovira A., Balasch M., Segalés J., García L., Plana-Durán J., Rosell C., Ellerbrok H., Mankertz A., Domingo M. 2002; Experimental inoculation of conventional pigs with porcine reproductive and respiratory syndrome virus and porcine circovirus 2. J Virol 76:3232–3239
    [Google Scholar]
  44. Salazar-Onfray F., Charo J., Petersson M., Freland S., Noffz G., Qin Z., Blankenstein T., Ljunggren H. G., Kiessling R. 1997; Down-regulation of the expression and function of the transporter associated with antigen processing in murine tumor cell lines expression IL-10. J Immunol 159:3195–3202
    [Google Scholar]
  45. Sarli G., Mandrioli L., Laurenti M., Sidoli L., Cerati C., Rolla G., Marcato P. S. 2001; Immunohistochemical characterization of the lymph node reaction in pig post-weaning multisystemic wasting syndrome (PMWS). Vet Immunol Immunopathol 83:53–67
    [Google Scholar]
  46. Sato K., Shibahara T., Ishikawa Y., Kondo H., Kubo M., Kadota K. 2000; Evidence of porcine circovirus infection in pigs with wasting disease syndrome from 1985 to 1999 in Hokkaido, Japan. J Vet Med Sci 62:627–633
    [Google Scholar]
  47. Segalés J., Sitjar M., Domingo M. 7 other authors 1997; First report of post-weaning multisystemic wasting syndrome in pigs in Spain. Vet Rec 141:600–601
    [Google Scholar]
  48. Segalés J., Pastor J., Cuenca R., Domingo M. 2000; Haematological parameters in post-weaning multisystemic wasting syndrome affected pigs. Vet Rec 146:675–676
    [Google Scholar]
  49. Segalés J., Alonso F., Rosell C. 10 other authors 2001; Changes in peripheral blood leukocyte populations in pigs with natural postweaning multisystemic wasting syndrome (PMWS). Vet Immunol Immunopathol 81:37–44
    [Google Scholar]
  50. Shibahara T., Sato K., Ishikawa Y., Kadota K. 2000; Porcine circovirus induces B lymphocyte depletion in pigs with wasting disease syndrome. J Vet Med Sci 62:1125–1131
    [Google Scholar]
  51. Smyth J. A., Moffat D. A., McNulty M. S., Todd D., Mackie D. A. 1993; A sequential histopathologic and immunocytochemical study of chicken anemia virus infection at one day of age. Avian Dis 37:324–328
    [Google Scholar]
  52. Todd D. 2000; Circoviruses: immunosuppressive threats to avian species: a review. Avian Pathol 29:373–394
    [Google Scholar]
  53. Weiss G. 2002; Interview about: interleukin-10 and anemia. Mod Aspects Immunobiol 2:206
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19124-0
Loading
/content/journal/jgv/10.1099/vir.0.19124-0
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