Expression of genes involved in the T cell signalling pathway in circulating immune cells of cattle 24 months following oral challenge with Bovine Amyloidotic Spongiform Encephalopathy (BASE)

Abstract

Background: Bovine Amyloidotic Spongiform Encephalopathy (BASE) is a variant of classical BSE that affects cows and can be transmitted to primates and mice. BASE is biochemically different from BSE and shares some molecular and histo-pathological features with the MV2 sub-type of human sporadic Creutzfeld Jakob Disease (sCJD).

Results: The present work examined the effects of BASE on gene expression in circulating immune cells. Ontology analysis of genes differentially expressed between cattle orally challenged with brain homogenate from cattle following intracranial inoculation with BASE and control cattle identified three main pathways which were affected. Within the immune function pathway, the most affected genes were related to the T cell receptor-mediated T cell activation pathways. The differential expression of these genes in BASE challenged animals at 10,12 and 24 months following challenge, vs unchallenged controls, was investigated by real time PCR.

Conclusions: The results of this study show that the effects of prion diseases are not limited to the CNS, but involve the immune system and particularly T cell signalling during the early stage following challenge, before the appearance of clinical signs.

Figure 1

Kinetics of expression for genes involved in the TCR pathway. Results from qPCR analysis of the expression of six genes (TRD, CD3E, TRAT, LAT, LCK, ZAP70) involved in TCR signaling in circulating immune cells, in control animals (T0) and BASE challenged animals at 10-12-24 months post challenge (T10, T12 and T14 respectively). Each column represents the mean ± SEM of at least three separate measurements on 4 individuals. The expression of mRNA normalized to two endogenous reference genes (β-Actin and β-2 Microglobulin), was analyzed by RT-PCR using specific primers as described in Material and Methods. The different superscripts indicate significant difference between columns (p < 0.01).