Evaluation of Gamma Interferon (IFN-γ)-Induced Protein 10 Responses for Detection of Cattle Infected with Mycobacterium bovis: Comparisons to IFN-γ Responses

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 by using archived samples from two aerosol inoculation studies. In the first study (104 CFU M. bovis by aerosol, n = 7), M. bovis purified protein derivative (PPDb)-specific IP-10 and IFN-gamma gene expression was detected as early as 29 days 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 = 0.87). In the second study (105 CFU M. bovis by aerosol, n = 5), IP-10 and IFN-gamma (protein) responses to mycobacterial antigens were compared following challenge. IFN-gamma responses to mycobacterial antigens were detected at 29 days after challenge and were sustained during the remainder of the study. IFN-gamma responses to mycobacterial antigens exceeded corresponding responses in nonstimulated cultures. IP-10 responses to mycobacterial antigens exceeded preinfection responses at 7, 29, and 63 days after challenge. In contrast to IFN-gamma responses, IP-10 responses to mycobacterial antigens generally did not exceed the respective responses in nonstimulated cultures. IP-10 responses to medium alone and to mycobacterial antigens followed a similar pattern of response. Correlations between IP-10 and IFN-gamma (protein) responses were modest (r approximate to 0.50 to 0.65). Taken together, these findings do not support the use of IP-10 protein as a biomarker for bovine tuberculosis using the current testing protocol and reagents; however, mRNA-based assays may be considered for further analysis.