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Title:   Author  item
                                            Thacker, Tyleritem
                                            Palmer, Mitchellitem
                                            Waters, Wade
  Submitted to: Meeting Abstract
                                    Publication Type: Abstract Only
                                    Publication Acceptance Date: 5/21/2007
                                    Publication  Date: 5/21/2007
                                    Citation: Thacker, T.C., Palmer, M.V., Waters, W.R. 2007. Associations between Cytokine Gene Expression and Pathology in Cattle infected with Mycobacterium bovis. [Abstract].  American Association for Microbiology. Abstract No. U-037.Interpretive Summary:
                                Technical Abstract: An impediment to the development of effective vaccines for bovine tuberculosis is the failure to demonstrate associations between immune function and protection. To investigate correlates of immunity, cytokine gene expression in response to Mycobacterium bovis infection (n = 10) were compared to responses by uninfected controls (n =5). Peripheral blood mononuclear cells (PBMC) were isolated and stimulated for 16 h with either M. bovis purified protein derivative, recombinant ESAT6:CFP10, or PBS for evaluation of gene expression using reverse-transcriptase real-time PCR. In addition, gene expression adjacent to gross lesions in the retropharyngeal LN was analyzed. Expression of IFN-gamma, TNF-alpha, iNOS and IL-4 by PBMC increased in response to infection, whereas, IL-10 expression decreased. Differences in gene expression between the PBMC from infected and uninfected animals were greatest at 30 days post-infection (dpi). Infected animals were divided into two groups based on pathology. PBMC from animals in the high pathology group expressed more IFN-gamma, TNF-alpha, iNOS and IL-4 than did animals in the low pathology group at early time points. Expression of these cytokines correlated with pathology 30 dpi. IL-10 gene expression decreased with time in PBMC from the high pathology group and was 2-fold less at 85 dpi. At this time point, IL-10 gene expression inversely correlated with pathology. IFN-gamma and iNOS gene expression were significantly greater in tissues from infected animals compared to tissues from uninfected animals. The pathological outcome of M. bovis infection of cattle may be established early after infection since expression of both the TH1 and TH2 cytokines correlated with pathology 30 dpi. In addition, more robust immunological responses correlated with increased pathology. These data suggest that early immune responses play a critical role in establishing the pathological outcome.


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