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Title:   Author  item
                                            Waters, Wadeitem
                                            Thacker, Tyleritem
                                            Nonnecke, Brianitem
                                            Palmer, Mitchellitem
                                            SCHILLER, I - Federal Veterinary Officeitem
                                            OESCH, B - Neurotune Agitem
                                            VORDERMEIER, H - Veterinary Laboratories Agency (VLA)item
                                            SILVA, E - Colorad0 State Universityitem
                                            ESTES, D - University Of Georgia
  Submitted to: Clinical and Vaccine Immunology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 12/29/2011
                                    Publication  Date: 3/1/2012
                                    Citation: Waters, W.R., Thacker, T.C., Nonnecke, B.J., Palmer, M.V., Schiller, I., Oesch, B., Vordermeier, H.M., Silva, E., Estes, D.M. 2012. Evaluation of gamma interferon (IFN-gamma)-induced protein 10 responses for detection of cattle infected with Mycobacterium bovis: comparisons to IFN-gamma responses. Clinical and Vaccine Immunology. 19(3):346-351.Interpretive Summary: Bovine tuberculosis (TB), caused by Mycobacterium bovis, has an important and adverse effect on socioeconomic, public health and trade of animals and animal products. The eradication of bovine TB in cattle is based on the detection and slaughter of infected animals or whole herds. Additional tools are needed to better diagnose TB in cattle. In the present study, a novel test for the detection of TB in cattle was evaluated. Knowledge obtained from this study may lead to an improved test for tuberculosis, thereby, advancing the national tuberculosis eradication program.
                                Technical Abstract: Gamma interferon (IFN-gamma)-induced protein 10 (IP-10) has recently shown promise as a diagnostic biomarker of Mycobacterium tuberculosis infection of humans. The aim of the current study was to compare IP-10 and IFN-gamma responses upon Mycobacterium bovis infection in cattle using archived samples from two aerosol inoculation studies. In the first study (10**4 cfu M. bovis, n = 7), M. bovis purified protein derivative (PPDb)-specific IP-10 and IFN-gamma gene expression were detected as early as 29d after challenge. PPDb-specific IP-10 and IFN-gamma mRNA responses followed a similar pattern of expression over the course of this study and were highly correlated (r = 0.852). In the second study (10**5 cfu M. bovis, n = 5), IP-10 and IFN-gamma (protein) responses to mycobacterial antigens were compared following challenge. IFN-gamma responses to mycobacterial antigens were detected 29d after challenge and were sustained during the remainder of the study. IFN-gamma responses to mycobacterial antigens exceeded corresponding responses in non-stimulated cultures. IP-10 responses to mycobacterial antigens exceeded pre-infection responses at 7d, 29d and 63d after challenge. In contrast to IFN-gamma, IP-10 responses to mycobacterial antigens generally did not exceed respective responses in non-stimulated cultures. IP-10 responses to media alone and to mycobacterial antigens followed a similar pattern of response. Correlations between IP-10 and IFN-gamma (protein) responses were modest (r  ̃ 0.50 – 0.65). Taken together, these findings do not support the use of IP-10 protein as a biomarker for bovine TB using the current testing protocol and reagents; however, mRNA-based assays may be considered for further analysis.


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