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

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  • 1 Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China;
  • | 2 Department of Dermatology and Venereology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China;
  • | 3 Department of Dermatology, The Third Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China
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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.

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Author Notes

Address correspondence to Dong-hua Liu, Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China. E-mail: ldhgxmu@163.com

These authors contributed equally to this work and share first authorship.

Financial support: This study was supported by the National Natural Science Foundation of China (81760564).

Authors’ addresses: Lin-xia Shen, Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, and Department of Dermatology and Venereology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China, E-mail: raja1010@sina.com. Di Yang, Department of Dermatology, The Third Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, E-mail: 645339219@qq.com. Ri-feng Chen and Dong-hua Liu, Department of Dermatology and Venereology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China, E-mails: 799928521@qq.com and ldhgxmu@163.com.

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