Abstract
Vaccination against paratuberculosis, a chronic disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (Map), has been considered as the most effective control method. However, protection is incomplete, and the mechanisms operating in the response of the animals to vaccination are not fully understood. Therefore, this study analyzed the immune response and the effects on protection against Map infection, elicited by paratuberculosis (Silirum®) and tuberculosis (heat-inactivated M. bovis [HIMB]) vaccines and their components in a caprine experimental model. Fifty goat kids were divided into 10 groups (n = 5) according to their vaccination (Silirum®, HIMB and nonvaccinated), immunization (inactivated bacteria or adjuvant), and/or infection. Oral challenge with Map was performed 45 days postvaccination/immunization (dpv), and animals were euthanized at 190 dpv. Peripheral immune response and proportion of lymphocyte subpopulations were assessed monthly by enzyme-linked immunosorbent assay and flow cytometry analysis, respectively. Local immune response, proportion of tissue lymphocyte subpopulations, Map detection (polymerase chain reaction), and histological examination were conducted in gut-associated lymphoid tissues. All infected groups developed paratuberculosis granulomatous lesions despite vaccination or immunization. The Silirum® and HIMB-vaccinated groups showed a considerable lesion reduction consistent with a significant peripheral cellular and humoral immune response. Besides, a lower number of granulomas were observed in groups immunized with inactivated bacteria and adjuvants in comparison to nonvaccinated and infected group. However, despite not being significant, this reduction was even higher in adjuvant immunized groups, which developed milder granulomatous lesion with no detectable peripheral immune responses associated with immunization. No changes in the peripheral and local proportion of lymphocyte subsets or local immune response were detected in relation to either vaccination/immunization or infection. Despite that paratuberculosis and tuberculosis vaccination showed a partial and cross-protection against Map infection, respectively, only histological examination could assess the progression of infection in these animals. In addition, the pattern observed in the reduction of the lesions in adjuvant immunized groups suggests the possible involvement of a nonspecific immune response that reduces the development of granulomatous lesions.
Highlights
Paratuberculosis is a chronic and debilitating disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (Map) [1] and responsible for significant global economic losses estimated at approximately US $12.61 million and $364.31 million in Spanish and European Union dairy cattle, respectively [2, 3]
Paratuberculosis lesions are characterized by small and well-demarcated granulomas, named focal or multifocal forms, located within the intestinal lymphoid tissue that can be seen in adult animals, where they are considered as forms of latency or resistance; disruption of the protective cell-mediated immune response leads to the development of diffuse lesions and the evolution toward a widespread granulomatous enteritis and the occurrence of clinical signs [7, 8]
Results are expressed as avian (A) and bovine (B) O.D. index values of each vaccination group (n = 5)
Summary
Paratuberculosis is a chronic and debilitating disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (Map) [1] and responsible for significant global economic losses estimated at approximately US $12.61 million and $364.31 million in Spanish and European Union dairy cattle, respectively [2, 3]. Initial protective immune response against Map has been related to a strong cell-mediated immune response characterized by the release of the proinflammatory cytokine interferon γ (IFN-γ), the formation of granulomas, and the clearance of the mycobacteria [5, 6]. In this sense, Map-infected animals can show a variety of lesions that have been shown to be closely related to the different phases of the disease. Pathological methods for paratuberculosis lesion characterization have been successfully applied in previous works as a reliable indicator of the presence of Map infection and the form of the disease shown by the infected animals [9–11]
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