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Differential cytokine gene expression profiles in the three pathological forms of sheep paratuberculosis.
BMC Vet Res. 2007 Aug 14; 3:18.BV

Abstract

BACKGROUND

Johne's disease is a chronic inflammatory disease of the gut caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP). Symptoms include wasting, diarrhoea, loss of condition and eventual death. Three forms of Johne's disease have been described in sheep - paucibacillary, multibacillary and asymptomatic. The paucibacillary form is characterized by an inflammatory, Th1-type immune response. The multibacillary form of the disease, which disseminates the infection, is characterized by macrophage infiltration mediated by a Th2-type immune response, and asymptomatic animals have no clinical symptoms or pathology but are infected with MAP. What determines these three forms of the disease is unknown. To further understand these differences, we used real-time RT-PCR to compare the expression of thirteen cytokine and cytokine-related genes in ileal tissue from sheep with the three forms of the disease.

RESULTS

Three pathological forms of sheep paratuberculosis were defined on the basis of histopathology, cytochemistry (Zeihl-Neelsen) and IS900 PCR. Paucibacillary lesions have largely T cell and eosinophil infiltration and are ZN negative; multibacillary lesions have macrophage infiltration and large numbers of acid-fast bacteria. The pauci- and multibacillary forms are linked to the differential expression of IFN gamma and IL-10 respectively. In addition the increased levels of the proinflammatory cytokines (IL-1 beta and TNFalpha), IL-8, IL-18 and TRAF-1 in both diseased forms is indicative of persistent inflammatory lesions. No changes were seen in IL-1 alpha in any sheep ileum tissues. Asymptomatic animals are IS900+ with normal histology but have significantly decreased levels of IL-18 and increased levels TNFalpha.

CONCLUSION

We have quantified the expression levels of thirteen cytokine and cytokine related genes in three forms of ovine paratuberculosis using real-time PCR analyses and confirm that sheep pauci- and multibacillary disease are linked to type 1 and type 2 T cell responses respectively. The expression patterns of other cytokines shows that both disease forms have an inflammatory aetiology but that the central role for IL-1 alpha in bovine paratuberculosis is not seen in the sheep infection. Asymptomatic animals are infected and show no pathology but can be distinguished, in terms of cytokine expression pattern, from uninfected controls.

Authors+Show Affiliations

Centre for Infectious Diseases, Royal (Dick) School of Veterinary Studies, Summerhall, Edinburgh, EH9 1QH, UK. j.a.smeed@sms.ed.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17697353

Citation

Smeed, Jennifer A., et al. "Differential Cytokine Gene Expression Profiles in the Three Pathological Forms of Sheep Paratuberculosis." BMC Veterinary Research, vol. 3, 2007, p. 18.
Smeed JA, Watkins CA, Rhind SM, et al. Differential cytokine gene expression profiles in the three pathological forms of sheep paratuberculosis. BMC Vet Res. 2007;3:18.
Smeed, J. A., Watkins, C. A., Rhind, S. M., & Hopkins, J. (2007). Differential cytokine gene expression profiles in the three pathological forms of sheep paratuberculosis. BMC Veterinary Research, 3, 18.
Smeed JA, et al. Differential Cytokine Gene Expression Profiles in the Three Pathological Forms of Sheep Paratuberculosis. BMC Vet Res. 2007 Aug 14;3:18. PubMed PMID: 17697353.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential cytokine gene expression profiles in the three pathological forms of sheep paratuberculosis. AU - Smeed,Jennifer A, AU - Watkins,Craig A, AU - Rhind,Susan M, AU - Hopkins,John, Y1 - 2007/08/14/ PY - 2007/05/16/received PY - 2007/08/14/accepted PY - 2007/8/19/pubmed PY - 2007/10/27/medline PY - 2007/8/19/entrez SP - 18 EP - 18 JF - BMC veterinary research JO - BMC Vet. Res. VL - 3 N2 - BACKGROUND: Johne's disease is a chronic inflammatory disease of the gut caused by infection with Mycobacterium avium subspecies paratuberculosis (MAP). Symptoms include wasting, diarrhoea, loss of condition and eventual death. Three forms of Johne's disease have been described in sheep - paucibacillary, multibacillary and asymptomatic. The paucibacillary form is characterized by an inflammatory, Th1-type immune response. The multibacillary form of the disease, which disseminates the infection, is characterized by macrophage infiltration mediated by a Th2-type immune response, and asymptomatic animals have no clinical symptoms or pathology but are infected with MAP. What determines these three forms of the disease is unknown. To further understand these differences, we used real-time RT-PCR to compare the expression of thirteen cytokine and cytokine-related genes in ileal tissue from sheep with the three forms of the disease. RESULTS: Three pathological forms of sheep paratuberculosis were defined on the basis of histopathology, cytochemistry (Zeihl-Neelsen) and IS900 PCR. Paucibacillary lesions have largely T cell and eosinophil infiltration and are ZN negative; multibacillary lesions have macrophage infiltration and large numbers of acid-fast bacteria. The pauci- and multibacillary forms are linked to the differential expression of IFN gamma and IL-10 respectively. In addition the increased levels of the proinflammatory cytokines (IL-1 beta and TNFalpha), IL-8, IL-18 and TRAF-1 in both diseased forms is indicative of persistent inflammatory lesions. No changes were seen in IL-1 alpha in any sheep ileum tissues. Asymptomatic animals are IS900+ with normal histology but have significantly decreased levels of IL-18 and increased levels TNFalpha. CONCLUSION: We have quantified the expression levels of thirteen cytokine and cytokine related genes in three forms of ovine paratuberculosis using real-time PCR analyses and confirm that sheep pauci- and multibacillary disease are linked to type 1 and type 2 T cell responses respectively. The expression patterns of other cytokines shows that both disease forms have an inflammatory aetiology but that the central role for IL-1 alpha in bovine paratuberculosis is not seen in the sheep infection. Asymptomatic animals are infected and show no pathology but can be distinguished, in terms of cytokine expression pattern, from uninfected controls. SN - 1746-6148 UR - https://www.unboundmedicine.com/medline/citation/17697353/Differential_cytokine_gene_expression_profiles_in_the_three_pathological_forms_of_sheep_paratuberculosis_ L2 - https://bmcvetres.biomedcentral.com/articles/10.1186/1746-6148-3-18 DB - PRIME DP - Unbound Medicine ER -