Talaromyces marneffei Influences Macrophage Polarization and Sterilization Ability via the Arginine Metabolism Pathway in Vitro

Abstract

The opportunistic fungal pathogen Talaromyces marneffei, which is endemic across a narrow band of tropical Southeast Asia and southern China, is an intracellular pathogen that causes systemic and lethal infection through the mononuclear phagocyte system. The mechanisms by which T. marneffei successfully replicates and escapes the immune system remain unclear. To investigate the role of arginine metabolism in the escape of T. marneffei from killer macrophages, we assessed inducible nitric oxide synthase (iNOS) and arginase expression, nitric oxide (NO) production, arginase and phagocytic activity, and the killing of T. marneffei in a coculture system. Our results indicate that T. marneffei induced macrophage polarization toward the M2 phenotype and regulated the arginine metabolism pathway by prolonging infection, thereby reducing antimicrobial activity and promoting fungal survival. Moreover, inhibiting T. marneffei–induced macrophage arginase activity with Nω-hydroxy-nor-arginine restored NO synthesis and strengthened fungal killing. These findings indicate that T. marneffei affects macrophage polarization and inhibits macrophage antimicrobial function via the arginine metabolism pathway.

Overexpression of CD86 enhances the ability of THP‐1 macrophages to defend against Talaromyces marneffei

“…The expression of CD86 is increased in the majority of early infection phases. However, compared to cells cultured alone, our earlier research indicated that the expression level of CD86 in macrophages was dramatically reduced, while the quantity of CD86 in the supernatant was significantly increased 11,12 . An important question that needs to be investigated is the role of CD86 in macrophage infection with T. marneffei ?…”

“…However, compared to cells cultured alone, our earlier research indicated that the expression level of CD86 in macrophages was dramatically reduced, while the quantity of CD86 in the supernatant was significantly increased. 11 , 12 An important question that needs to be investigated is the role of CD86 in macrophage infection with T. marneffei ? Many pattern recognition receptors of macrophages can directly interact with fungi, leading to the production of macrophage inflammatory cytokines.…”

“…However, compared to cells cultured alone, our earlier research indicated that the expression level of CD86 in macrophages was dramatically reduced, while the quantity of CD86 in the supernatant was significantly increased. 11,12 An…”

“…Additionally, polarization of the M1 macrophages was insufficient and they polarized to M2 macrophages. 11,12 To withstand the lethal impact of macrophages, T. marneffei may adsorb or take up CD86 in the supernatant produced by them when they come into contact with THP-1 cells. Therefore, we hypothesized that increasing CD86 on macrophages might enhance immunity against T. marneffei.…”

“…The level of CD86 expression in macrophages considerably dropped as infection progressed in a time‐dependent manner, while the amount of CD86 in the supernatant significantly increased. Additionally, polarization of the M1 macrophages was insufficient and they polarized to M2 macrophages 11,12 . To withstand the lethal impact of macrophages, T. marneffei may adsorb or take up CD86 in the supernatant produced by them when they come into contact with THP‐1 cells.…”