Immunoresponsive gene 1 facilitates TLR4 agonist-induced augmentation of innate antimicrobial immunity.

ABSTRACT: Treatment with the toll-like receptor 4 agonist monophosphoryl lipid A conditions innate immunocytes to respond robustly to subsequent infection, a phenotype termed innate immune memory. Our published studies show that metabolic reprogramming of macrophages is a prominent feature of the memory phenotype. We undertook studies to define the functional contributions of tricarboxylic acid cycle reprogramming to innate immune memory. We observed that priming of wild-type mice with monophosphoryl lipid A potently facilitated accumulation of the tricarboxylic acid cycle metabolite itaconate at sites of infection and enhanced microbial clearance. Augmentation of itaconate accumulation and microbial clearance was ablated in Irg1-deficient mice. We further observed that monophosphoryl lipid A potent

SUBMITTER: McBride MA 

PROVIDER: S-EPMC11879002 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature