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The immunopathology of paucibacillary and multibacillary sheep paratuberculosis is characterized by inflammatory T cell and macrophage responses respectively. IL-23 and IL-25 are key to the development of these responses by interaction with their complex receptors, IL-23R/IL-12RB1 and IL-17RA/IL-17RB. In humans, variations in structure, sequence and/or expression of these genes have been implicated in the different pathological forms of tuberculosis and leprosy, and in gastrointestinal inflammatory disorders such as Crohn’s disease. Sequencing has identified multiple transcript variants of sheep  IL23R ,  IL12RB1  and  IL17RB  and a single  IL17RA  transcript. RT-qPCR assays were developed for all the identified variants and used to compare expression in the ileo-caecal lymph node of sheep with paucibacillary or multibacillary paratuberculosis and uninfected animals. With IL-23 receptor, only the  IL12RB1v3  variant, which lacks the receptor activation motif was differentially expressed and was significantly increased in multibacillary disease; this may contribute to high Th2 responses. Of the  IL17RB  variants only full length  IL17RB  was differentially expressed and was significantly increased in multibacillary pathology; which may also contribute to Th2 polarization.  IL17RA  expression was significantly increased in paucibacillary disease. The contrast between the  IL17RA  and  IL17RB  results may indicate that, in addition to Th1 cells, Th17 T cells are also involved in paucibacillary pathology.   Electronic supplementary material  The online version of this article (doi:10.1186/s13567-016-0314-4) contains supplementary material, which is available to authorized users.

Variations in IL-23 and IL-25 receptor gene structure, sequence and expression associated with the two disease forms of sheep paratuberculosis