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Title:   Author  item
                                            Thacker, Tyleritem
                                            Palmer, Mitchellitem
                                            Waters, Wade
  Submitted to: Keystone Symposia
                                    Publication Type: Proceedings
                                    Publication Acceptance Date: 1/19/2004
                                    Publication  Date: 4/5/2004
                                    Citation: Thacker, T.C., Palmer, M.V., Waters, W.R. 2004. White-tailed deer (odocoileus virginianus) cytokine expression in response to infection with mycobacterium bovis. Proceedings of Keystone Symposia. p.119.Interpretive Summary:
                                Technical Abstract: Mycobacterium bovis is the primary cause of tuberculosis in animals. Free ranging white-tailed deer (WTD) in Michigan were found to be infected with M. bovis, representing a natural reservoir that poses a threat to cattle and humans. In addition, WTD are more susceptible to M. bovis infection than other deer species. Despite the importance of this reservoir little is known about host defense mechanisms triggered by M. bovis infection of WTD. To characterize these immune responses, 11 yearling white-tailed deer were inoculated intratonsilarly with 600 cfu M. bovis. Five uninfected animals served as controls. At 4 week intervals lymphocytes were isolated and cultured with media alone, M. bovis PPD, or a recombinant fusion protein composed of ESAT6 and CFP10. Sixteen hours later RNA was isolated, reverse-transcribed then assessed for cytokine gene expression using real-time PCR. Relative differences were calculated using the 2delta/deltaCt method. At 8 weeks post infection the relative expression of IFN-gamma and IL-12p40 were 72 and 2 fold higher, respectively, than uninfected controls. At 16 weeks post infection the relative level of IFN-gamma was 117 fold greater in infected animals compared to the uninfected controls and IL-12p40 was approximately 3.7 fold greater. In contrast to these TH1 cytokines no significant difference between the infected and uninfected controls was detected for the TH2 cytokines IL-4 and IL-10 until 16 weeks post infection. At 16 weeks post infection IL-4 and IL-10 were 3 and 2 fold greater, respectively. No significant differences were detected for GM-CSF, iNOS or TGF-ß when comparing infected vs uninfected animals. These data suggest that initially there is a strong TH1 response. However as infection proceeds TH2 cytokines begin to be expressed, suggesting that a switch toward a TH2 response may be occurring. This may explain in part why white-tailed deer fail to control infection.


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