Essential Role of MHC II in the Antitubercular Efficacy of Pyrazinamide.

ABSTRACT: Antibacterial drug mechanisms have traditionally been examined through a drug-pathogen lens, often overlooking the host's role in shaping drug activity. However, growing evidence suggests that the host environment is crucial for antibacterial efficacy. Pyrazinamide (PZA), a key component of modern tuberculosis therapy, exemplifies this complexity-exhibiting potent in vivo activity despite its inability to reduce Mycobacterium tuberculosis viability in standard in vitro culture. Here, using macrophage and murine infection models, we identify a critical role for host cell-mediated immunity in PZA's antitubercular action. Through the use of MHC II knockout mice, we demonstrate that CD4 T cell help is essential for PZA efficacy. Notably, while IFN-γ is required for PZA-med

SUBMITTER: Lamont EA 

PROVIDER: S-EPMC12393548 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature