ArticleFrontiers in immunology2026
Monophosphoryl lipid A boosts macrophage antimicrobial immunity by metabolically regulating source-specific ROS generation.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Monophosphoryl lipid A (MPLA), a toll-like receptor (TLR) 4 agonist and licensed vaccine adjuvant, reprograms innate immune cells to confer protection against diverse pathogens. However, the metabolic and molecular adaptations supporting this response remain poorly defined. Methods: The contributions of discrete reactive oxygen species (ROS) sources-including NADPH oxidase 2 (NOX2), xanthine oxidase (XO), mitochondria, and inducible nitric oxide synthase (iNOS)-to MPLA-induced macrophage antimicrobial activity were examined using genetic deletion or pharmacologic inhibition. Metabolic and redox adaptations supporting this response were assessed by analyzing oxidative pentose phosphate pathway (oxPPP) activity, glutathione-dependent antioxidant systems, and mitochondrial oxidative phosphorylation in MPLA-primed macrophages. Results: MPLA enhanced macrophage clearance of Conclusion: These findings define the metabolic and redox circuits driving MPLA-induced antimicrobial immunity and establish its potential as a host-directed antimicrobial therapy beyond vaccine adjuvancy.
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