IL-1-driven stromal cell response to Mycobacterium tuberculosis in mouse lungs

However, tuberculosis pathogenesis remains poorly understood and is not fully recapitulated in standard mouse models. Here we report that a comparison across three different susceptible mouse models identifies Mtb-induced gene signatures that predict active TB disease in humans significantly better than a signature from the standard C57BL/6 mouse model.

Common to signatures from susceptible mice were myeloid cell response and immunosuppressive genes. In line with the signatures, an increase in lung myeloid cells, including neutrophils, was conserved across the susceptible mouse models, mimicking the neutrophilic inflammation observed in humans. Myeloid cells in the susceptible models and non-human primates exhibited high expression of immunosuppressive molecules including IL-1 receptor antagonist, which inhibits IL-1 signaling.