Differential expression of pattern recognition receptors in the three pathological forms of sheep paratuberculosis

Paratuberculosis is a chronic inflammatory disease of the gut caused by Mycobacterium avium subspecies paratuberculosis. Three forms have been described in sheep--paucibacillary, multibacillary and asymptomatic. The pauci- and multibacillary forms are characterized by type 1 and type 2 immune responses respectively; asymptomatic animals have no clinical signs or pathology. What determines this polarization is unknown, although pattern recognition receptors (PRR) have been implicated in other mycobacterial diseases. To investigate this in sheep paratuberculosis we used real-time RT-PCR to quantify the expression of fifteen PRR and adaptor genes from forty infected and nine control animals. These data show that there is a relationship between the different pathological forms and PRR transcript profiles. Nine PRRs were up-regulated in asymptomatic animals; with TLR9 being significantly raised in relation to the other three groups. Comparison of the three infected groups showed increases in many PRRs, with CARD15 and Dectin-2 being particularly high in both diseased groups. Significant differences between the pauci- and multibacillary animals included TLR2, CD14 and Dectin-1. Sequence analysis of TLR2 exon 2 and CARD15 exon 11 in the forty animals failed to identify any relationship between SNPs and pathological form.