L-arginine (ARG) availability is a critical determinant of macrophage antimicrobial capacity, as it fuels nitric oxide production and other immune effector pathways essential for restricting Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). L-citrulline (CIT), a precursor in the ARG regeneration cycle, can replenish intracellular ARG pools when transport is limited.
However, the comparative and combined effects of exogenous ARG and/or CIT on intracellular Mtb control across macrophage lineages and activation states remain insufficiently defined. This study investigated how supplementation with ARG, CIT or their combination influences Mtb survival in human and murine, primary macrophages and cell line, both in naïve and IFNγ-activated states, and evaluated whether these amino acids can enhance the activity of anti-TB drugs, isoniazid (INH) and rifampicin (RIF).
Across a 5-day infection course, both ARG and CIT significantly reduced intracellular Mtb loads relative to untreated cells, with high-dose supplementation eliciting earlier and more sustained inhibition. These effects were amplified in IFNγ-stimulated macrophages, accelerating Mtb control and minimizing dose-dependent differences.
Frontiers in Immunology published a clinical update in Infectious Disease on 05 May 2026.
The item focuses on Impact of L-arginine and L-citrulline supplementation on macrophage responses to Mycobacterium tuberculosis.
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