Inflammasome Activation Differences Underpin Different <i>Mycobacterium tuberculosis</i> Infection Outcomes.

ABSTRACT: The clinical outcome of Mycobacterium tuberculosis (Mtb) infection ranges from latent/nonprogressive disease to active/progressive tuberculosis (TB), but the cellular events contributing to these variable outcomes remain unknown. Here, we report that progressive Mtb infection is associated with upregulation of guanylate-binding protein-1 (GBP1), hypoxia-inducible factor-1 alpha (HIF-1α), and elevated NLR family pyrin domain-containing (NLRP3) inflammasome activation pathways. Using rabbit lungs and primary rabbit and human macrophages, as well as human monocytic THP-1-derived macrophages for infection with Mtb strains (H₃₇Rv, HN878, or CDC1551) that differ in virulence, we show that NLRP3 inflammasome activation by HIF-1α and GBP1 leads to elevated mitochondrial stress, a

SUBMITTER: Kumar R 

PROVIDER: S-EPMC12640619 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature