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Title:   Author  item
                                            Waters, Wadeitem
                                            Miller, Janiceitem
                                            Palmer, Mitchellitem
                                            Stabel, Judithitem
                                            JONES, D - IOWA STATE UNIVitem
                                            KOISTINEN, K - IOWA STATE UNIVitem
                                            STEADHAM, E - IOWA STATE UNIVitem
                                            HAMILTON, M - WASH. STATE UNIVitem
                                            DAVIS, W - WASH. STATE UNIVitem
                                            Bannantine, John
  Submitted to: Infection and Immunity
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 6/7/2003
                                    Publication  Date: 9/1/2003
                                    Citation: Waters, W.R., Miller, J.M., Palmer, M.V., Stabel, J.R., Jones, D.E., Koistinen, K.A., Steadham, E.M., Hamilton, M.J., Davis, W.C., Bannantine, J.P. 2003. Experimental mycobacterium avium subsp. paratuberculosis infection of calves: early induction of a humoral and cellular immune response. Infection and Immunity. 71:5130-5138.Interpretive Summary: Johne's disease of cattle is ubiquitous causing serious economic losses to the dairy industry due to decreased health and production of affected animals. A major impediment in the study of this disease is the lack of a reproducible experimental model of infection in the target hose (i.e., cattle). In the present study we describe a method to infect very young cattle with the bacterium that causes this serious disease. In addition, we describe the immune response induced by infection in these animals. Findings from the present study will be useful for the development of improved methods to diagnose and prevent this chronic disease of cattle.
                                Technical Abstract: Johne's disease (paratuberculosis) of cattle is widespread and causes significant economic losses for producers due to decreased production and poor health of affected animals. The chronic nature of the disease and the lack of a reproducible model of infection hinder research efforts. In the present study, instillation of Mycobacterium avium subsp. paratuberculosis into the tonsillar crypts of neonatal calves resulted in chronic infection with peripheral colonization detected by ante-mortem culture of feces and post-mortem (320 d postchallenge) culture of intestinal tissues. Antigen-specific blastogenic, IFN-g, and nitric oxide responses by blood mononuclear cells from infected calves exceeded prechallenge responses beginning 194 d postchallenge. Upon in vitro stimulation with paratuberculosis antigens, CD4**+ cells from infected calves proliferated, produced IFN-g, and increased expression of CD26 and CD45RO (i.e., indicative of an activated memory phenotype). Utilizing a lipoarabinomannan-based ELISA, specific serum immunoglobulin was detected as early as 134 d postchallenge and generally increased after this time point. Two antigens of ~50-kDa and ~60-kDa were particularly immunodominant early in infection as shown by immunoblot with serum collected within 2 weeks postchallenge. Findings indicate that the intratonsillar inoculation route will prove useful as an experimental model for paratuberculosis pathogenesis, diagnosis, and vaccine efficacy studies. Additionally, this study confirms that mycobacteria-specific antibody is detectable early in the course of experimental Johne's disease, even preceeding the development of specific cell-mediated responses


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