Interleukin-1 receptor antagonist is a conserved early factor for exacerbating tuberculosis susceptibility.

ABSTRACT: Mycobacterium tuberculosis (Mtb) causes 1.25 million deaths a year. However, tuberculosis (TB) pathogenesis remains poorly understood and is not fully recapitulated in standard mouse models. Here we find that gene signatures from three different Mtb-susceptible mouse models predict active TB disease in humans significantly better than a signature from resistant C57BL/6 (B6) mice. Conserved among susceptible mice, non-human primates, and humans, but largely absent from B6 mice, was Mtb-induced differentiation of macrophages into an Spp1 ⁺ differentiation state. Spp1 ⁺ macrophages expressed high levels of immunosuppressive molecules including IL-1 receptor antagonist (IL-1Ra). IL-1Ra was previously reported to cause Mtb s

SUBMITTER: Lee OV 

PROVIDER: S-EPMC10634924 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature