Immunopathology of early and subclinical Mycobacterium avium subspecies paratuberculosis infection in calves

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This research is designed to enhance our understanding of host innate immunity and resistance to mycobacterial infection. I am interested in how interactions between host innate immune cells and invading mycobacteria influence the outcome of infection. Mycobacterium avium subspecies paratuberculosis (Map) causes Johne's disease, an important and costly intestinal disease affecting beef and dairy cattle in Canada and around the world. Global efforts to control mycobacterial infections including Map have achieved limited success and this is largely because the fundamental mechanisms leading to success (elimination of infection) or failure (establishment of persistent infection) of host immunity are unknown. Gamma-delta T lymphocytes are a unique class of innate immune cells that have been recently implicated as orchestrators of host defense by directing adaptive immunity which is known to be essential for clearance of invading mycobacteria. We have observed recruitment of gamma-delta T cells to Map infection sites in calves, but a mechanistic understanding of their function in host immunity has not been elucidated. In these studies, we will investigate how these innate cells direct host immunity during initial Map infection: 1) how they are recruited to early infection sites and 2) how they affect function of other immune cells (macrophages, dendritic cells) which are vital for success of host immunity. We will also examine gamma-delta T cells within the intestine of calves with subclinical intestinal Map infection, and how they direct either maintenance of persistent infection (latency) or progression to clinical disease. The results will lead to improved strategies to reduce mycobacterial infections and identify subclinically-infected individuals as well as enhanced recognition of the role of innate immune cells in controlling bacterial infections.