Talaromyces marneffei promotes M2-like polarization of human macrophages by downregulating SOCS3 expression and activating the TLR9 pathway. Issue 1 (1st January 2021)

• Record Type: Journal Article
• Authors: Wei, Wudi; Ning, Chuanyi; Huang, Jiegang; Wang, Gang; Lai, Jingzhen; Han, Jing; He, Jinhao; Zhang, Hong; Liang, Bingyu; Liao, Yanyan; Le, Thuy; Luo, Qiang; Li, Zhen; Jiang, Junjun; Ye, Li; Liang, Hao
• Is Part Of: Virulence. Volume 12:Issue 1(2021)
• Page Start: 1997
• Page End: 2012
• Publication Date: 2021-01-01
• Subjects: Talaromyces marneffei -- macrophages -- M2 polarization -- SOCS3 -- TLR9 pathway; Virulence (Microbiology) -- Periodicals; Bacterial diseases -- Periodicals; Molecular microbiology -- Periodicals; 579.05
• DOI: 10.1080/21505594.2021.1958470
• Languages: English
• ISSNs: 2150-5608

Abstract

ABSTRACT: Little is known about how Talaromyces marneffei, a thermally dimorphic fungus that causes substantial morbidity and mortality in Southeast Asia, evades the human immune system. Polarization of macrophages into fungal-inhibiting M1-like and fungal-promoting M2-like types has been shown to play an important role in the innate immune response against fungal pathogens. This mechanism has not been defined for T. marneffei . Here, we demonstrated that T. marneffei promotes its survival in human macrophages by inducing them toward M2-like polarization. Our investigations of the mechanism revealed that T. marneffei infection led to SOCS3 protein degradation by inducing tyrosine phosphorylation, thereby relieving the inhibitory effect of SOCS3 on p-STAT6, a key factor for M2-like polarization. Our SOCS3-overexpression experiments showed that SOCS3 is a positive regulator of M1-like polarization and plays an important role in limiting M2-like polarization. Furthermore, we found that inhibition of the TLR9 pathway partially blocked T. marneffei -induced M2-like polarization and significantly enhanced the killing activity of macrophages against T. marneffei . Collectively, these results reveal a novel mechanism by which T. marneffei evades the immune response of human macrophages.