Proceedings of the 10th International Colloquium on Paratuberculosis

#23
Role <strong>of</strong> Mycobacterium avium. subsp. paratuberculosis in <strong>the</strong> pathogenesis <strong>of</strong>
Crohn’s disease
William C. Davis, Andrew J Allen, Mary Jo Hamilton, Gaber S Abdellrazeq, Heba M. Rihan,
George M. Barrington, Kevin L. Lahmers, Kun T Park, Srinand Sreevatsan, Christopher Davies
Washington State University, USA; University <strong>of</strong> Minnesota, USA; Utah State University
Crohn’s disease (CD) is a clinically defined syndrome <strong>of</strong> unknown etiology. Patients with CD develop chronic
relapsing bouts <strong>of</strong> enteritis. The mechanisms <strong>of</strong> induction and persistence <strong>of</strong> inflammation appear to include
modulation <strong>of</strong> <strong>the</strong> immune response through activation <strong>of</strong> <strong>the</strong> IL-23/IL-17 and IL-22 pathways that promote
chronic inflammation. Factors that trigger CD are thought to include exposure to specific pathogens, bacteria
present in normal micr<strong>of</strong>lora <strong>of</strong> <strong>the</strong> intestine, or o<strong>the</strong>r undefined factors that induce persistent immune mediated
inflammation <strong>of</strong> <strong>the</strong> bowel. Mycobacterium avium subsp. paratuberculosis (Map) <strong>the</strong> etiological agent <strong>of</strong>
Johne’s disease (JD) is <strong>the</strong> pathogen most frequently implicated in CD immunopathogenesis. The finding <strong>of</strong>
Map in many patients with CD supports this possibility. It remains unclear, however, how Map could be involved
in CD pathogenesis. Elucidation <strong>of</strong> <strong>the</strong> mechanisms <strong>of</strong> pathogenesis mediated by Map in its natural host could
provide insight into its potential role in CD pathogenesis. We developed a bovine ileal cannulation model to analyze
<strong>the</strong> mechanisms <strong>of</strong> JD immunopathogenesis. The studies revealed animals become persistently infected
following exposure to Map with no signs <strong>of</strong> clinical disease during <strong>the</strong> first year post infection (PI). Map elicited
a prominent CD4 T cell response to Map and Map antigens 3 months PI. A similar response was observed in
animals at <strong>the</strong> clinical stage <strong>of</strong> disease. The CD8 T cell response was more prominent in animals at <strong>the</strong> clinical
stage <strong>of</strong> disease. Quantitative RT-PCR revealed a complex pattern <strong>of</strong> expression <strong>of</strong> genes encoding IFN-γ, IL-
17, IL-22, and granulysin PI indicating <strong>the</strong> presence <strong>of</strong> CD4 T cells associated with a Type I immune response
and Th17 and Th22 CD4 T cells associated with a proinflammatory response. The findings show that persistent
infection with Map could play a role in CD pathogenesis.
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