Differential Requirements for l-Citrulline and l-Arginine during Antimycobacterial Macrophage Activity

摘要: Microbicidal NO production is reliant on inducible synthase-mediated L-arginine metabolism in macrophages (MΦs). However, supply can be restricted by arginase activity, resulting inefficient output and inhibition of antimicrobial MΦ function. MΦs circumvent this converting L-citrulline to L-arginine, thereby resupplying substrate for production. In article, we define the metabolic signature mycobacteria-infected murine supplied L-citrulline, or both amino acids. Using liquid chromatography-tandem mass spectrometry, determined that synthesized from was less effective as a arginase-mediated L-ornithine compared with directly imported extracellular milieu. Following Mycobacterium bovis bacillus Calmette-Guerin infection costimulation IFN-γ, observed activity did not inhibit derived contrary witnessed when were cultured L-arginine. Furthermore, found arginase-expressing preferred over promotion antimycobacterial activity. We expect defining consequences will provide novel approaches enhancing immunity, especially context mycobacterial disease.