Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 1/15/2011
Publication Date: 3/2/2011
Citation: Stabel, J.R., Robbe-Austerman, S. 2011. Early immune markers associated with experimental Mycobacterium avium subsp. paratuberculosis (MAP) infection in a neonatal calf model. Clinical and Vaccine Immunology. 18:393-405. 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 evaluate different methods of experimental infection in a calf model. Further, we discuss the results of infection on the presence of the bacteria in tissues along with the associated damage to the tissue. Results of this study suggest that experimental infection of calves by the oral method resulted in an increased number of bacteria in the tissues. This type of study will aid in the evaluation of new vaccines to prevent infection and disease.
Technical Abstract: The objective of this study was to observe early markers of cell-mediated immunity in naïve calves infected with Mycobacterium avium subsp. paratuberculosis (MAP) and how expression of these markers evolved over the 12-month period of infection. Methods of experimental infection included: Control (noninfected); Oral (MAP strain K-10); Oral/DXM (pretreatment with dexamethasone before oral inoculation); IP (intraperitoneal inoculation); and Oral/M (oral inoculation with mucosal scrapings from a cow with clinical disease). One of the earliest markers to emerge was antigen-specific interferon-g (IFN-g). IP calves had earliest detectable antigen-specific IFN-' responses at 7 d post-infection, followed by other infection groups at 90 and 120 d, with very robust responses noted for all infection groups throughout the remainder of the study. At 1 month, Oral and Oral/M calves had higher MPS-stimulated interleukin-10 (IL-10) than other treatment groups but IL-10 secretion declined by 12 months for all calves. T cell activation markers such as CD25, CD26, CD45RO, and CD5 were significantly upregulated in infected calves compared to noninfected controls. Oral inoculation of calves resulted in significantly increased antigen-specific lymphocyte proliferation at 9 and 12 months post-infection, as well as iNOS secretion at 6 and 12 months post-infection. These results demonstrate that infection of naïve calves with MAP will invoke early immunologic responses characterized by robust antigen-specific IFN-g responses and induction of CD25 and CD45RO expression on T cell subsets. This was followed by antigen-specific lymphocyte proliferation, iNOS, and expression of CD26 and CD5bright markers in the latter part of the 12-month study.