Jejunal mucosal immune response in goats ten months after <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> challenge is primarily determined by lesion severity rather than vaccination route

Current vaccines against paratuberculosis offer incomplete and variable protection that raises questions on the ruminant immune responses to Mycobacterium avium subspecies paratuberculosis (Map) infection, particularly at the mucosal level. Thus, this study examined the immune responses established in the jejunum of goats vaccinated with oral, intradermal, or subcutaneous inactivated vaccines 11 months post-vaccination and 10 months after experimental Map challenge. In general terms, the mucosal response of non-challenged animals was not affected by vaccination. However, the quantification of immune cell populations, cytokine expression, recall responses of tissue-isolated mononuclear leukocytes, and secretory IgA levels in vaccinated and challenged animals with focal lesions suggested a local Th1 polarization. In contrast, those with diffuse lesions exhibited features compatible with the early development of a more Th2-biased response. The vaccination route played a lesser role in the immune response than lesion severity. Orally vaccinated and challenged goats, showed reduced local IL-1β and IL-17A expression, which may explain the milder lesions observed in these animals, despite their high bacterial burden, as these cytokines participate in macrophage recruitment, granuloma formation, and bacterial clearance. Nevertheless, owing to the high variability among challenged animals, larger sample sizes would allow robust conclusions to be drawn in further studies.