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Two different forms of clinical paratuberculosis in sheep are recognised, related to the level of bacterial colonization. Paucibacillary lesions are largely composed of lymphocytes with few bacteria, and multibacillary pathology is characterized by heavily-infected macrophages. Analysis of cytokine transcripts has shown that inflammatory Th1/Th17 T cells are associated with development of paucibacillary pathology and Th2 cytokines are correlated with multibacillary disease. The master regulator T cell transcription factors  TBX21 ,  GATA3 ,  RORC2  and  RORA  are critical for the development of these T cell subsets. Sequence variations of the transcription factors have also been implicated in the distinct disease forms of human mycobacterial and gastrointestinal inflammatory diseases. Relative RT-qPCR was used to compare expression levels of each transcript variant of the master regulators in the ileo-caecal lymph nodes of uninfected controls and sheep with defined paucibacillary and multibacillary pathology. Low levels of  GATA3  in multibacillary sheep failed to confirm that multibacillary paratuberculosis is caused simply by a Th2 immune response. However, high levels of  TBX21 ,  RORC2  and  RORC2v1  highlights the role of Th1 and Th17 activation in paucibacillary disease. Increased  RORAv1  levels in paucibacillary tissue suggests a role for RORα in Th17 development in sheep; while elevated levels of  RORAv4  hints that this variant might inhibit RORα function and depress Th17 development in multibacillary sheep.   Electronic supplementary material  The online version of this article (doi:10.1186/s13567-016-0368-3) contains supplementary material, which is available to authorized users.

Variations in T cell transcription factor gene structure and expression associated with the two disease forms of sheep paratuberculosis