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

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 successf...

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Detalles Bibliográficos
Autores principales: Shen, Lin-xia, Yang, Di, Chen, Ri-feng, Liu, Dong-hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society of Tropical Medicine and Hygiene 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9490654/
https://www.ncbi.nlm.nih.gov/pubmed/35895344
http://dx.doi.org/10.4269/ajtmh.21-0568
Descripción
Sumario: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 N(ω)-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.