Comparison of sheep, goats, and calves as infection models for Mycobacterium avium subsp. paratuberculosis

Authors: Stabel, Judith; Bannantine, John; HOESTETTER, J - Iowa State University

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/6/2020
Publication Date: 4/21/2020
Citation: Stabel, J.R., Bannantine, J.P., Hoestetter, J.M. 2020. Comparison of sheep, goats, and calves as infection models for Mycobacterium avium subsp. paratuberculosis. Veterinary Immunology and Immunopathology. 225(110060). https://doi.org/10.1016/j.vetimm.2020.110060.
DOI: https://doi.org/10.1016/j.vetimm.2020.110060

Interpretive Summary: Johne's disease is a chronic, debilitating intestinal disorder in cattle, sheep and wild ruminants, characterized by diarrhea, reduced feed intake, weight loss and death. Animals usually become infected when they are young by ingesting feces containing the causative bacteria. Animal infection models are necessary for the study of host responses to infection under controlled conditions. In this paper, we present results from a study designed to compare lambs, goats, and calves as experimental infection models. The benefit to a smaller ruminant in the model would be decreased cost to the researcher for housing and care. However, we need to confirm that a smaller ruminant would be comparable to the bovine model. In the paper we discuss the results of oral infection on the presence of the bacteria in tissues and differences in the immune responses to infection. Results of this study suggest that experimental infection of calves is the most desirable infection model for use in our research. Optimization of animal infection models will aid in the evaluation of new vaccines and therapeutics to prevent and treat infection and disease.

Technical Abstract: Animal infection models to study Mycobacterium avium subsp. paratuberculosis (MAP) infection are useful for evaluating the efficacy of vaccines and other therapeutics for the prevention or treatment of infection. The goal of the present study was to compare smaller ruminants, sheep and goats, with calves as infection models. Neonatal sheep, goats, and calves (nequal4) received 10 to the forth power 9 cfu of a cattle isolate of MAP in milk replacer on days 0, 3 and 6 in a 12-month study and sampled monthly thereafter. Results demonstrated a robust antigen-specific IFN-' response at 90 days post-inoculation for sheep and goats, with lower responses noted for calves. By 360 days, IFN-gamma responses were 50 and 82 percent higher for calves than for goats and sheep, respectively. Although MAP-specific antibody responses were first observed in sheep at 90 days, calves had higher antibody responses throughout the remainder of the study. Following pass-through shedding on day 7, fecal shedding was fairly negligible across treatments but remained higher for calves throughout the study. Colonization of tissues was variable within treatment group and was higher for calves and sheep for the majority of tissues. Upon antigen stimulation of PBMCs, higher populations of CD4plus T cells cells and lower populations of gamma/delta TCRplus and NK cells were observed for goats and calves compared to sheep. Relative gene expression of IL-4, IL-12, and IL-17 in PBMCs was higher in goats, corresponding to lower tissue colonization with MAP. These data suggest that ruminant species are fairly comparable as infection models for MAP, but discrete differences in host responses to MAP infection exist between species.