TLR2/MyD88/NF-B signalling pathway regulates IL-8 production in porcine alveolar macrophages infected with porcine circovirus 2 Free

Abstract

Porcine circovirus 2 (PCV2) is the primary cause of post-weaning multisystemic wasting syndrome, in which it stimulates a strong IL-8 response that is associated with chronic inflammation as well as lesions in the lymphoid organs. However, the mechanism underlying PCV2-induced IL-8 production is still unclear. In the present study, we demonstrated that increased IL-8 expression during PCV2 infection depends on Toll-like receptor (TLR2), but not TLR4 or TLR9 signalling pathways in porcine alveolar macrophages. Moreover, we found that impairment of the MyD88/NF-κB signalling pathway by MyD88 knockdown or NF-κB inhibitors markedly decreased PCV2-induced IL-8 secretion. These results suggest that PCV2 induces IL-8 secretion via the TLR2/MyD88/NF-κB signalling pathway. Therefore, it is important to elucidate the molecular mechanisms of the PCV2-induced inflammatory response.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000345
2016-02-01
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/97/2/445.html?itemId=/content/journal/jgv/10.1099/jgv.0.000345&mimeType=html&fmt=ahah

References

  1. Akira S., Uematsu S., Takeuchi O. 2006; Pathogen recognition and innate immunity. Cell 124:783–801 [View Article]
    [Google Scholar]
  2. Arce C., Ramirez-Boo M., Lucena C., Garrido J. J. 2010; Innate immune activation of swine intestinal epithelial cell lines (IPEC-J2 and IPI-2I) in response to LPS from Salmonella typhimurium . Comp Immunol Microbiol Infect Dis 33:161–174 [View Article]
    [Google Scholar]
  3. Baggiolini M., Clark-Lewis I. 1992; Interleukin-8, a chemotactic and inflammatory cytokine. FEBS Lett 307:97–101 [View Article]
    [Google Scholar]
  4. Bi J., Song S., Fang L., Wang D., Jing H., Gao L., Cai Y., Luo R., Chen H., Xiao S. 2014; Porcine reproductive and respiratory syndrome virus induces IL-1β production depending on TLR4/MyD88 pathway and NLRP3 inflammasome in primary porcine alveolar macrophages. Mediators Inflamm 2014:403–515 [View Article]
    [Google Scholar]
  5. Borghetti P., Morganti M., Saleri R., Ferrari L., De Angelis E., Cavalli V., Cacchioli A., Corradi A., Martelli P. 2013; Innate pro-inflammatory and adaptive immune cytokines in PBMC of vaccinated and unvaccinated pigs naturally exposed to porcine circovirus type 2 (PCV2) infection vary with the occurrence of the disease and the viral burden. Vet Microbiol 163:42–53 [View Article]
    [Google Scholar]
  6. Brown R. A., Gralewski J. H., Eid A. J., Knoll B. M., Finberg R. W., Razonable R. R. 2010; R753Q single-nucleotide polymorphism impairs Toll-like receptor 2 recognition of hepatitis C virus core and nonstructural 3 proteins. Transplantation 89:811–815 [View Article]
    [Google Scholar]
  7. Calsamiglia M., Fraile L., Espinal A., Cuxart A., Seminati C., Martin M., Mateu E., Domingo M., Segales J. 2007; Sow porcine circovirus type 2 (PCV2) status effect on litter mortality in postweaning multisystemic wasting syndrome (PMWS). Res Vet Sci 82:299–304 [View Article]
    [Google Scholar]
  8. Chae C. 2005; A review of porcine circovirus 2-associated syndromes and diseases. Vet J 169:326–336 [View Article]
    [Google Scholar]
  9. Chae J. S., Choi K. S. 2011; Proinflammatory cytokine expression in the lung of pigs with porcine circovirus type 2-associated respiratory disease. Res Vet Sci 90:321–323 [View Article]
    [Google Scholar]
  10. Choi C., Chae C. 2000; Distribution of porcine parvovirus in porcine circovirus 2-infected pigs with postweaning multisystemic wasting syndrome as shown by in-situ hybridization. J Comp Pathol 123:302–305 [View Article]
    [Google Scholar]
  11. Costa H., Nascimento R., Sinclair J., Parkhouse R. M. 2013; Human cytomegalovirus gene UL76 induces IL-8 expression through activation of the DNA damage response. PLoS Pathog 9:e1003609 [View Article]
    [Google Scholar]
  12. Darwich L., Balasch M., Plana-Duran J., Segales J., Domingo M., Mateu E. 2003a; Cytokine profiles of peripheral blood mononuclear cells from pigs with postweaning multisystemic wasting syndrome in response to mitogen, superantigen or recall viral antigens. J Gen Virol 84:3453–3457 [View Article]
    [Google Scholar]
  13. Darwich L., Pie S., Rovira A., Segales J., Domingo M., Oswald I. P., Mateu E. 2003b; Cytokine mRNA expression profiles in lymphoid tissues of pigs naturally affected by postweaning multisystemic wasting syndrome. J Gen Virol 84:2117–2125 [View Article]
    [Google Scholar]
  14. Devhare P. B., Chatterjee S. N., Arankalle V. A., Lole K. S. 2013; Analysis of antiviral response in human epithelial cells infected with hepatitis E virus. PLoS One 8:e63793 [View Article]
    [Google Scholar]
  15. Duan D., Zhang S., Li X., Guo H., Chen M., Zhang Y., Han J., Lv Y. 2014; Activation of the TLR/MyD88/NF-κB signal pathway contributes to changes in IL-4 and IL-12 production in piglet lymphocytes infected with porcine circovirus type 2 in vitro . PLoS One 9:e97653 [View Article]
    [Google Scholar]
  16. Fu Y., Quan R., Zhang H., Hou J., Tang J., Feng W. H. 2012; Porcine reproductive and respiratory syndrome virus induces interleukin-15 through the NF-κB signaling pathway. J Virol 86:7625–7636 [View Article]
    [Google Scholar]
  17. Ge Y., Mansell A., Ussher J. E., Brooks A. E., Manning K., Wang C. J., Taylor J. A. 2013; Rotavirus NSP4 triggers secretion of proinflammatory cytokines from macrophages via Toll-like receptor 2. J Virol 87:11160–11167 [View Article]
    [Google Scholar]
  18. Gilmore T. D. 2006; Introduction to NF-κB: players, pathways, perspectives. Oncogene 25:6680–6684 [View Article]
    [Google Scholar]
  19. Hernández J. C., Stevenson M., Latz E., Urcuqui-Inchima S. 2012; HIV type 1 infection up-regulates TLR2 and TLR4 expression and function in vivo and in vitro . AIDS Res Hum Retroviruses 28:1313–1328 [View Article]
    [Google Scholar]
  20. Hoffmann E., Dittrich-Breiholz O., Holtmann H., Kracht M. 2002; Multiple control of interleukin-8 gene expression. J Leukocyte Biol 72:847
    [Google Scholar]
  21. Kawai T., Akira S. 2010; The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11:373–384 [View Article]
    [Google Scholar]
  22. Ketchum P. A., Novitsky T. J. 2000; Assay of endotoxin by limulus amebocyte lysate. Methods Mol Med 36:3–12
    [Google Scholar]
  23. Koch A. E., Polverini P. J., Kunkel S. L., Harlow L. A., DiPietro L. A., Elner V. M., Elner S. G., Strieter R. M. 1992; Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 258:1798–1801 [View Article]
    [Google Scholar]
  24. Kunkel S. L., Standiford T., Kasahara K., Strieter R. M. 1991; Interleukin-8 (IL-8): the major neutrophil chemotactic factor in the lung. Exp Lung Res 17:17–23 [View Article]
    [Google Scholar]
  25. Li W., Liu S., Wang Y., Deng F., Yan W., Yang K., Chen H., He Q., Charreyre C., Audoneet J. C. 2013; Transcription analysis of the porcine alveolar macrophage response to porcine circovirus type 2. BMC Genomics 14:353 [View Article]
    [Google Scholar]
  26. Lv Y., Zhang X., Sun Y., Zhang S. 2013; Activation of NF-κB contributes to production of pig-major acute protein and serum amyloid A in pigs experimentally infected with porcine circovirus type 2. Res Vet Sci 95:1235–1240 [View Article]
    [Google Scholar]
  27. Mahe Y., Mukaida N., Kuno K., Akiyama M., Ikeda N., Matsushima K., Murakami S. 1991; Hepatitis B virus X protein transactivates human interleukin-8 gene through acting on nuclear factor κB and CCAAT/enhancer-binding protein-like cis-elements. J Biol Chem 266:13759–13763
    [Google Scholar]
  28. Marks F. S., Reck J. J. Jr, Almeida L. L., Berger M., Correa A. M., Driemeier D., Barcellos D. E., Guimaraes J. A., Termignoni C., Canal C. W. 2010; Porcine circovirus 2 (PCV2) induces a procoagulant state in naturally infected swine and in cultured endothelial cells. Vet Microbiol 141:22–30 [View Article]
    [Google Scholar]
  29. Mavrommatis B., Offord V., Patterson R., Watson M., Kanellos T., Steinbach F., Grierson S., Werling D. 2014; Global gene expression profiling of myeloid immune cell subsets in response to in vitro challenge with porcine circovirus 2b. PLoS One 9:e91081 [View Article]
    [Google Scholar]
  30. Rathinam V. A. K., Fitzgerald K. A. 2011; Innate immune sensing of DNA viruses. Virology 411:153–162 [View Article]
    [Google Scholar]
  31. Takeda K., Akira S. 2004; TLR signaling pathways. Semin Immunol 16:3–9 [View Article]
    [Google Scholar]
  32. Wensvoort G., Terpstra C., Pol J. M., ter Laak E. A., Bloemraad M., de Kluyver E. P., Kragten C., van Buiten L., den Besten A., other authors. 1991; Mystery swine disease in The Netherlands: the isolation of Lelystad virus. Vet Q 13:121–130 [View Article]
    [Google Scholar]
  33. Zhang H., Liu C., Cheng S., Wang X., Li W., Charreyre C., Audonnet J. C., He Q. 2013; Porcine CD74 is involved in the inflammatory response activated by nuclear factor kappa B during porcine circovirus type 2 (PCV-2) infection. Arch Virol 158:2285–2295 [View Article]
    [Google Scholar]
  34. Zhou Q., Fan H., Liu Z. 2010; MyD88 knockdown by liposome-mediated RNA interference to porcine monocyte-derived dendritic cell. Chinese J Cell Biol 32:415–421
    [Google Scholar]
  35. Zhu Y., Lau A., Lau J., Jia Q., Karuppannan A. K., Kwang J. 2007; Enhanced replication of porcine circovirus type 2 (PCV2) in a homogeneous subpopulation of PK15 cell line. Virology 369:423–430 [View Article]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000345
Loading
/content/journal/jgv/10.1099/jgv.0.000345
Loading

Data & Media loading...

Most cited Most Cited RSS feed