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Title:   Author  item
                                            Thacker, Tyleritem
                                            Palmer, Mitchellitem
                                            Waters, Wade
  Submitted to: Clinical and Vaccine Immunology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 4/11/2006
                                    Publication  Date: 6/1/2006
                                    Citation: Thacker, T.C., Palmer, M.V., Waters, W.R. 2006. Correlation of Cytokine Gene Expression with Pathology in White-Tailed Deer (Odocoileus virginianus) Infected with Mycobacterium bovis. Clinical and Vaccine Immunology.  13(6):640-647.Interpretive Summary: Tuberculosis in white-tailed deer (WTD) was discovered in northeastern Michigan in 1994. Subsequent surveys revealed that a small percentage of the free-ranging WTD population was infected. These infected WTD may serve as a source of bacteria that may infect domestic cattle, farmed WTD and humans. Reduction and elimination of this repository of infected animals is vital to the U.S. Bovine Eradication Program. Understanding how the bacteria cause disease and how the WTD immune systems works to prevent disease may be essential to the development of an effective vaccine. This study reports that WTD with greater disease produced more of a protein called Interferon gamma (IFN-g). IFN-g is a protein messenger that causes the immune system to become active and destroy the bacteria. IFN-g produced by the immune system is currently being used as an aid in diagnosing animals that are infected with the bacteria that cause tuberculosis. WTD with less severe disease produced less IFN-g than did the animals with more severe disease. Another protein messenger produced by cells of the immune system, IL-4, was shown to moderate disease. The animals with less severe disease produced more IL-4 than animals with more severe disease. This finding contradicts research in other species where it has been reported that IL-4 production was associated with more disease. These findings provide data which may be used to evaluate the effectiveness of vaccine candidates.
                                Technical Abstract: Mycobacterium bovis infected white-tailed deer (WTD) were detected in northeast Michigan in 1994. Subsequent surveys revealed a focus of infection that represents the first known reservoir of M. bovis in North America. Relatively little work has been done to characterize the immune response of white-tailed deer to M. bovis. It was hypothesized that a TH1 response would result in less severe pathology. M. bovis infected and uninfected deer were monitored for cytokine mRNA expression and pathology. Infected WTD expressed significantly more IFN-gamma, IL-12p40, GM-CSF, iNOS and IL-4 mRNA than did the uninfected controls, however, no significant differences were detected in the expression of IL-10 and TGF-beta. Animals could be divided into two groups based on their pathology. In animals with less severe pathology, lesions were primarily confined to the lymph nodes of the head. Lesions in the lymph nodes of the head and lung characterized animals with more severe pathology. Contrary to the hypothesis, IFN-gamma expression correlated with greater pathology. PBMC from animals in the high pathology group produced on average 2.75 times more IFN-gamma mRNA than animals in the low pathology group. IL-4 expression was greater in the low pathology group than in the high pathology group. These data suggest that TH1 responses in WTD play a role in both protection and pathogenesis of M. bovis.


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