Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/28/2011
Publication Date: 7/1/2011
Citation: Stabel, J.R., Bannantine, J.P., Eda, S., Robbe-Austerman, S. 2011. Induction of B Cell responses upon experimental infection of neonatal calves with Mycobacterium avium subsp. paratuberculosis. Clinical and Vaccine Immunology. 18(7):1139-1149. 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 induction of immune responses mediated by B cells. Results of this study suggest that experimental infection of calves by the oral method invoked significant responses by B cells. This type of study will aid in the evaluation of new vaccines to prevent infection and disease.
Technical Abstract: Animal models are useful for studying host responses to infection and aid in the development of diagnostic tools and vaccines. The current study was designed to compare the effects of different methods of experimental infection: Oral (Mycobacterium avium subsp. parauberculosis (MAP) strain K-10; Oral/DXM (pretreatment with dexamethasone before oral inoculation with strain K-10); IP (intraperitoneal inoculation with strain K-10); and Oral/M (oral inoculation with mucosal scrapings from a clinical cow) in neonatal calves. The objective of this study was to determine if infection with MAP over 12-month period would invoke changes in the percentages of total B cells in the peripheral blood mononuclear cell population and in subpopulations of B cells as determined by CD5, CD25, and CD45RO markers. Over the course of the study, the percentage of total B cells in nonstimulated and antigen-stimulated cell cultures increased (P < 0.01) for orally and intraperitoneally infected calves, with the highest percentages noted at 3 and 6 months post-infection. Oral infection of calves with a clinical strain of MAP (Oral/M) resulted in increased percentages of CD5dim and CD5bright B cells, regardless of in vitro stimulation, by 9 and 12 months post-infection. Experimental infection by all methods resulted in increased expression of CD25+B cells and CD45RO+ B cells early in the study but the most significant results were observed at 12 months for calves pre-treated with dexamethasone before oral inoculation with strain K-10 (Oral/DXM) and Oral/M calves. Immunoblot analyses demonstrated the greatest reactivity to a whole-cell sonicate of MAP in sera from IP calves and the lowest was observed in calves orally inoculated with strain K-10. Further evidence of strong MAP-specific antibody responses in the IP calves was demonstrated using the EvELISA method. In summary, the method of experimental inoculation with MAP did affect the induction of B cell subpopulations and the appearance of MAP-specific antibody during the 12-month study period.