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Project Leader:
Johne’s Disease: Pathogenesis and control of Mycobacterium avium subspecies
paratuberculosis
Members Background Objectives Progress

Project Leader:

Project Leader:

VIDO research program area: Emerging Disease & Microbial Virulence

Overview:
Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease. Some infected animals are able to clear the organism, indicating that innate and/or acquired immunity can be effective, while other animals become persistently infected and shed the organism into the environment. These pathogens can subvert the hosts’ immune system and reside inside macrophages, a cell that normally kills ingested bacteria. We are undertaking genomic, proteomic and functional studies which will support research on the effect of immunomodulating compounds on macrophages. This will enable us to determine whether the activation of specific immune pathways can overcome the suppressive effect of MAP which in turn will offer new targets for intervention using conventional therapeutic measures as well as vaccination studies.

Background:
Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease in cattle. While the cost of Johne's disease in beef herds is not well described, nearly 40 per cent of dairy herds in Ontario tested positive at least once for Johne’s disease. A Canadian study in 2002 found that Johne’s disease caused the highest average production loss among five production-limiting diseases, costing Canadian farmers almost $2,500 for every 50-cow herd each year (Chi et al. 2002. Prev Vet Med 55, 157-53).

These studies will fill a fundamental gap in our knowledge of MAP pathogenesis, specifically regarding the bacterial components involved in causing disease and the host response in relevant cell types, enabling vaccine development.

Despite the enormous health impacts of Mycobacterium species in a variety of hosts, only one vaccine--a live-attenuated version--has been widely utilized. The difficulty in the development of new vaccines has been attributed to the complex nature of mycobacterial infections and the bacterium’s ability to reside within cells of the host’s immune system.

The long-term objectives of this project are to use genomic and proteomic technologies to elucidate the interaction between MAP and the immune system of cattle and to identify subunit vaccine formulations which will protect cattle against colonization by this organism.

It is our hypothesis that MAP interferes with normal host innate immune responses through the production of novel effector molecules which could form the basis for the development of vaccine formulations and vaccination strategies.

Objectives:
The specific objectives of this project include:
1. Determine the response (genomic, proteomic and kinomic) of ileal macrophages and peripheral blood mononuclear cells to infection with MAP.
2. Determine the response (genomic, proteomic and kinomic) of calves to infection with MAP using an intestinal loop model.
3. Determine the ability of various immunomodulators to activate macrophages for MAP killing.
4. Determine if mucosal immunization in the intestine results in protection against MAP infection.

Progress:
1. We have optimized the growth conditions for MAP and performed initial infections of freshly isolated bovine monocytes.
2. We have optimized peptide arrays for kinomic analysis of infected bovine monocytes.

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