Comparative cellular immune responses in calves after infection with Mycobacterium avium subsp. paratuberculosis, M. avium subsp. avium, M. kansasii and M. bovis

Authors: Stabel, Judith; WATERS, W - Retired ARS Employee; Bannantine, John; Palmer, Mitchell

Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/8/2021
Publication Date: 7/1/2021
Publication URL: https://handle.nal.usda.gov/10113/7377001
Citation: Stabel, J.R., Waters, W.R., Bannantine, J.P., Palmer, M.V. 2021. Comparative cellular immune responses in calves after infection with Mycobacterium avium subsp. paratuberculosis, M. avium subsp. avium, M. kansasii and M. bovis. Veterinary Immunology and Immunopathology. 237. https://doi.org/10.1016/j.vetimm.2021.110268.
DOI: https://doi.org/10.1016/j.vetimm.2021.110268

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. However, symptoms of disease do not usually present themselves until the animals reach 3 to 5 years of age or even older. During this time the animal is infected and may be shedding the organism in its feces without showing any clinical signs of disease. In addition to reduced production by these animals through reduced milk production, they also present a potential infective threat to the rest of the herd. Johne’s disease is difficult to diagnose and therefore to control. 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 characterize host immunity in calves infected with closely related mycobacterial pathogens. Further, we discuss the results of infection on the induction of specific immune responses mediated by T and B cells. Results of this study suggest that experimental infection of calves with different mycobacteria can result in disparate immune responses. This type of study will aid in the evaluation of diagnostic tools to detect mycobacterial infections in the field.

Technical Abstract: In the present study, calves were infected with Mycobacterium avium subsp. paratuberculosis (MAP), Mycobacterium avium subsp. avium (M. avium), Mycobacterium kansasii (M. kansasii), or Mycobacterium bovis (M. bovis) to determine differences in cellular immunity. Comparative cellular responses were assessed upon stimulation of cells with mycobacterial whole cell sonicates respective of each infection group. Antigen-specific whole blood interferon gamma (IFN-gamma) responses were observed in all infection groups compared to noninfected control calves, however, responses were more robust for M. bovis calves. Upon antigen stimulation of PBMCs, secretion of IFN-gamma and IL-10 was higher for M. bovis calves compared to other infection groups. In contrast, IL-12 secretion was lower for M. bovis calves compared to MAP infected calves. Within the total PBMC population, higher numbers of CD4plus, CD8plus, and gamma delta TCR plus T cells were observed for MAP and M. avium calves compared to M. bovis calves. This aligned with higher expression of CD26 on these subpopulations for MAP and M. avium calves, as well. In contrast, greater expression of CD25 was observed on CD4plus and gamma delta TCRplus T cells and natural killer cells for M. bovis calves. Overall, similarities in cellular immune responses were observed between the closely related MAP and M. avium during infection of calves. In contrast, significant differences were noted between calves infected with MAP and M. bovis. This suggests that host immune responses to different mycobacteria may impact interpretation of diagnostic tools based upon their cellular immunity.