Upregulation of IL-17A, CXCL9 and CXCL10 in Early-Stage Granulomas Induced by Mycobacterium bovis in Cattle
Article first published online: 22 AUG 2012
© 2012 Crown copyright. Reproduced with the permission of the Controller of Her Majesty's Stationery Office/Queen's Printer for Scotland and Animal Health and Veterinary Laboratories Agency.
Transboundary and Emerging Diseases
Volume 60, Issue 6, pages 525–537, December 2013
How to Cite
Aranday-Cortes, E., Bull, N. C., Villarreal-Ramos, B., Gough, J., Hicks, D., Ortiz-Peláez, Á., Vordermeier, H. M. and Salguero, F. J. (2013), Upregulation of IL-17A, CXCL9 and CXCL10 in Early-Stage Granulomas Induced by Mycobacterium bovis in Cattle. Transboundary and Emerging Diseases, 60: 525–537. doi: 10.1111/j.1865-1682.2012.01370.x
- Issue published online: 6 NOV 2013
- Article first published online: 22 AUG 2012
- Manuscript Received: 1 JUN 2012
- Defra. Grant Number: SE3227
- European Community's Seventh Framework programme (FP7/2007/2013). Grant Number: 228394
- Wellcome Trust
- Mycobacterium bovis ;
- laser capture microdissection;
To gain further insight into the immunopathogenesis of bovine tuberculosis (bTB), the cytokine and chemokine expression of cattle experimentally infected with Mycobacterium bovis was analysed in TB granulomas, using immunohistochemistry (IHC) and laser capture microdissection (LCM) followed by qPCR. Immunohistochemistry was conducted for cell types using labelling for CD68, CD3, CD4, CD8, WC1 and CD79a and for the cytokines IFN-γ, TNF-α and TGF-β as well as inducible form of nitric oxide synthase (iNOS). qPCR was conducted for mRNA expression of IFN-γ, TNF-α, TGF-β, IL-17A, IL-22, IL-2, granzyme A and the chemokines CXCL9 and CXCL10. Early stages of granuloma were primarily comprised of epithelioid MΦs expressing high levels of IFN-γ and iNOS, with significantly upregulated expression of CXCL9 and CXCL10 when compared with control tissue. These chemokines displayed a trend of decreasing mRNA expression as lesion progressed, suggesting a higher level of importance during the early stages of the immune response to mycobacterial infection. IL-22 levels showed a strong trend of decrease through granuloma development, and IL-17A was shown to be upregulated, supporting its investigation as a potential biomarker of bTB. The use of LCM and qPCR may prove especially useful for the study of IL-17A as previous attempts to analyse its expression using IHC and in situ hybridization proved unsuccessful.