The Mechanism of Talaromyces Marneffei Influencing Macrophage RAW264.7 Polarization and Sterilization Ability via Arginine Metabolism Pathway

Abstract

Background The opportunistic fungi T. marneffei is an intracellular pathogen that causes systemic and lethal infection through the mononuclear phagocyte system. Macrophages act as pacesetters to resist pathogen invasion and communicators to activate adaptive immunity. During infection, macrophages induce iNOS to generate NO, which kills invading pathogenic microorganisms. Arginase competes with the iNOS for a common substrate L-arginine. We tried to investigate the effect of arginine metabolism on the escape of T. marneffei from macrophage killing. Results We performed qPCR, immunobolt detection, immunofluorescent staining, arginase activity assay and NO production assay when macrophages were co-cultured with T. marneffei. We conducted immunobolt detection, arginase activity assay, NO production assay, phagocytic activity assay and T. marneffei killing assay after adding the arginase specific inhibitor nor-NOHA to the co-culture system. T. marneffei decreased the NO production in macrophages by increasing macrophage arginase activity. With lastingness of infection, T. marneffei induced macrophages towards M2 phenotype polarization, thereby reducing antimicrobial activity and promoting fungal survival. Moreover, inhibiting the T. marneffei-induced macrophage arginase activity with nor-NOHA restored NO synthesis and strengthened the function of fungal killing. Conclusions T. marneffei potentiated its own survival via regulating arginine metabolism pathway in macrophages during an infection.