Development of immune-biomarkers of pulmonary tuberculosis in a rabbit model

SummaryTuberculosis (TB) causes extensive morbidity and mortality worldwide with approximately 10 million new cases of active disease emerging mostly from a pool of two billion individuals latently infected with Mycobacterium tuberculosis (M. tb) every year. The underlying host immune responses that drive M. tb infection to active disease or latency are not well understood. We propose that identification and characterization of host immune biomarkers will be helpful to better understand the mechanisms that drive this process, and may, in addition, lead to the development of better diagnostic tools for TB. We have previously reported the profiles of plasma immune biomarkers in pulmonary TB patients in endemic countries, and in M. tb-infected nonhuman primates. However, biomarker profiling for a cost-effective and user-friendly animal model relevant to human disease, such as rabbit, has not been developed. One challenge in the analysis of circulating cytokines/chemokines for rabbit model of TB is the limited availability of validated immune-reagents. Here we report the use of a commercially available multiplex microbead human cytokine/chemokine panels as development platform for rabbit immune reagents. The results demonstrate their utility to determine circulating analytes and define their profiles related to TB in the rabbit model. In addition, we report the profiles of circulating anti-M. tb antibodies in the plasma of rabbits with active pulmonary TB. These studies show that the pattern of expression of circulating immune biomarkers correlate with TB pathology in rabbits, and are similar to those defined in pulmonary TB patients.