A contained Mycobacterium tuberculosis mouse infection model predicts active disease and containment in humans

Previous studies have identified whole-blood transcriptional risk and disease signatures for Tuberculosis (TB); however, several lines of evidence suggest that these signatures primarily reflect bacterial burden, which increases prior to symptomatic disease. We found that the peripheral blood transcriptome of mice with contained Mycobacterium tuberculosis infection (CMTB) has striking similarities to that of humans with active TB and that a signature derived from these mice predicts human disease with comparable accuracy to signatures derived directly from humans. A set of genes associated with immune defense are upregulated in CMTB mice but not in humans with active TB suggesting that their upregulation is associated with bacterial containment. A signature comprised of these genes predicts both protection from TB disease and successful treatment at early time points where current signatures are not predictive. These results suggest that detailed study of the CMTB mouse model may enable identification of biomarkers for human TB