Evaluation of antigen specific interleukin-1β as a biomarker to detect cattle infected with Mycobacterium bovis

Abstract

Bovine tuberculosis (bTB) is a major world-wide health problem that has been difficult to control, due to the lack of an effective vaccine and limited ability of the tuberculin skin test (TST) and the ancillary whole blood interferon-gamma (IFN-γ) release assay (IGRA) to detect all infected animals. A 6 h cytokine flow cytometric IFN-γ (CFC) assay was developed in effort to overcome these limitations and expand methods for studying the mechanisms of bTB immunopathogenesis. The present study was conducted to evaluate IL-1β as a biomarker to use in conjunction with the IFN-γ CFC assay to improve the diagnostic accuracy for bTB. Three animal groups with predefined Mbv infection status were used for analysis of IL-1β in plasma from whole blood cultures stimulated with ESAT-6/CFP-10 for 20-24 h. Parallel stimulations were performed for enumeration of IFN-γ producing T cells. Data analysis showed that Mbv infected animals have a higher frequency of IFN-γ producing CD4+ T cells and plasma IL-1β than animals exposed to non-tuberculous mycobacteria (NTM) or uninfected control animals, with a significant correlation between the two readouts, thus allowing differentiation between the three animal groups. IL-1β has the potential to serve as an additional biomarker for detecting cattle infected with Mbv.