Blood RNA signature predicts recent tuberculosis exposure in mice

Knowing when a person was infected with Mycobacterium tuberculosis (M.tb) is critical as recent infection is the strongest clinical risk factor for progression to TB disease in immunocompetent individuals. However, time since M.tb infection is very difficult to determine in routine clinical practice. We determined whether gene expression patterns in blood RNA correlate with time since M.tb infection or exposure to develop a biomarker for recent exposure. As proof of concept, we found an RNA signature that accurately discriminated early and late time periods after experimental infection in mice. Blood was collected from 20 C57BL/6 mice infected with a low dose of M.tb (Erdman), as well as 6 uninfected age-matched control mice. Blood was collected at days 30, 60, 90, 120 and 150 post-infection. Whole blood was subjected to microarray analysis. We identify a gene expression signature that predicts infection time point.