Resilience to infection by Mycobacterium avium subspecies paratuberculosis following direct intestinal inoculation in calves

Mycobacterium avium subspecies paratuberculosis (Map) is the cause of Johne's disease, a chronic enteritis of cattle. A significant knowledge gap is how persistence of Map within the intestinal tract after infection contributes to progression of disease. To address this, we exposed calves to Map by direct ileocecal Peyer's patch injection. Our objective was to characterize the persistence of Map in tissues, associated intestinal lesions, fecal Map shedding, and serum antibody responses, through the first 28-weeks post-inoculation (wpi). Previous work using this model showed 100% rate of Map infection in intestine and lymph node by 12 wpi. We hypothesized that direct inoculation of Map into the distal small intestine would induce intestinal Map infection with local persistence and progression towards clinical disease. However, our data show decreased persistence of Map in the distal small intestine and draining lymph nodes. We identified Map in multiple sections of distal ileum and draining lymph node of all calves at 4 and 12 wpi, but then we observed reduced Map in distal ileum at 20 wpi, and by 28 wpi we found that 50% of animals had no detectable Map in intestine or the lymph node. This provides evidence of resilience to Map infection following direct intestinal Map inoculation. Further work examining the immune responses and host-pathogen interactions associated with this infection model are needed to help elicit the mechanisms underlying resilience to Map infection.