Dual infections with Mycobacterium avium ss. paratuberculosis and bovine leukemia virus alter regulatory T cell prevalence and activity in cattle. (160.12)

Abstract

Abstract Johne’s disease (paratuberculosis) is a chronic disease of domestic ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP) that currently ranks as one of the most costly diseases in the U.S. Dairy Industry. We proposed that the chronic nature of Johne’s disease would result in development of regulatory T cells (Tregs). Tregs would shift immune responses away from a pro-inflammatory Th1 to an unproductive Th2 response. In the course of studies on Tregs and MAP, we uncovered a confounding effect due to bovine leukemia virus (BLV) infection. Healthy control cattle displayed significant FoxP3 (Tregs) staining in mesenteric lymph nodes, but lymph nodes from BLV infected cattle were devoid of FoxP3 expressing cells. Concurrent infection with MAP partially restores FoxP3 expressing cell populations. BLV infection also reduces TGFβ (2-fold reduction) mRNA abundance in mesenteric lymph nodes, while concurrent infection with MAP partially restores TGFβ mRNA levels. In peripheral blood mononuclear cells, BLV infection reduces abundance of TGFβ, but dramatically enhances abundance of IL-10 mRNA. Taken together, our results suggest that BLV alters immune profiles to favor progression of MAP infection. Recent estimates suggest over 83% of U.S. dairy operations are currently positive for BLV and approximately 68% are positive for MAP. If concurrent infection with these two pathogens increases losses due to MAP, then the economic consequences could be staggering.