Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 25, 2013
Publication Date: June 1, 2013
Repository URL: http://handle.nal.usda.gov/10113/56814
Citation: Stabel, J.R., Waters, W.R., Bannantine, J.P., Palmer, M.V. 2013. Disparate host immunity to Mycobacterium avium subsp. paratuberculosis antigens in calves inoculated with M. avium subsp. paratuberculosis, M. avium subsp. avium, M. kansasii and M. bovis. Clinical and Vaccine Immunology. 20(6):848-857. 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 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 to antigen preparations. 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: Cross-reactivity of mycobacterial antigens in immune-based diagnostic assays has been a major concern and criticism of current tests for the detection of paratuberculosis. In the present study, host immune responses to antigen preparations of Mycobacterium avium subsp. paratuberculosis (MAP), consisting of a whole-cell sonicate (MPS), as well as pools of MAP recombinant proteins, were compared in calves experimentally infected with live MAP, M. avium subsp. avium (M. avium), M. kansasii, and M. bovis. Interferon-gamma (IFN-gamma) responses to MPS were observed in all infected calves, regardless of pathogen, compared to control noninfected calves at 4 months post-infection. Pooled recombinant MAP proteins also elicited non-specific IFN-gamma responses in infected calves, with the exception of M. bovis calves. Interestingly, M. bovis calves had significantly higher interleukin-10 (IL-10) and lower IL-12 responses to MPS compared to other calves. A significant upregulation of CD25 and CD26 expression was noted on CD4, CD8 and gamma-delta T cell subpopulations, as well as B cells, for calves infected with either MAP or M. avium after antigen stimulation of cells. Stimulation with MPS also resulted in increased expression of CD26 on CD45RO+CD25+ T cells from MAP and M. avium infected calves. Recombinant MAP proteins failed to elicit antigen-specific responses for the majority of parameters measured. Results suggest that host immune responses for MAP and M. avium infections in young calves are closely aligned but somewhat disparate from responses in M. bovis infection in calves.