Johne’s disease in cattle – pathogenesis and control of Mycobacterium avium subspecies paratuberculosis
Mycobacterium avium subspecies paratuberculosis (MAP) is the causative agent of Johne’s Disease and has been linked, although not definitively, to Crohn’s Disease in humans. Although some infected animals are able to clear the organism, MAP has the ability to subvert the immune system by hiding in ileal macrophages resulting in persistently infected animals that shed the organism into the environment.
To improve the understanding of MAP pathogenesis, research is focused on genomic and proteomic functional studies to examine the interaction between MAP and ileal Peyer’s Patch macrophages using both isolated cells and whole animals. Kinome analysis will also be used to analyze macrophage signaling pathways. These studies will form a basis for studying the effect of immunomodulatory compounds on macrophages which are designed to determine if the activation of specific pathways can overcome the suppressive effect of MAP. This, in turn, will offer new targets for intervention using conventional therapeutic measures as well as vaccination studies. Furthermore, we are currently using a reverse vaccinology approach to develop novel vaccine candidates for both Johne’s disease and bovine tuberculosis.
- Determine the kinomic response monocytes to infection with MAP
- Determine the response (immune and kinomic) of calves to infection with MAP using an intestinal loop model
- Determine the ability for various immunomodulators to activate macrophages for MAP killing
- Determine if local immunization results in protection against MAP
- Reverse vaccinology approach to vaccine development for MAP and M. bovis