Talaromyces marneffei promotes M2-like polarization of human macrophages by downregulating SOCS3 expression and activating the TLR9 pathway.
Talaromyces marneffei promotes M2-like polarization of human macrophages by downregulating SOCS3 expression and activating the TLR9 pathway.
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DOI：
10.1080/21505594.2021.1958470
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发表时间：
2021-12
期刊：
影响因子：
5.2
通讯作者：
Liang H
中科院分区：
文献类型：
--
作者：
Wei W;Ning C;Huang J;Wang G;Lai J;Han J;He J;Zhang H;Liang B;Liao Y;Le T;Luo Q;Li Z;Jiang J;Ye L;Liang H
很少有人知道Talaromyces marneffei，一种在东南亚引起大量发病率和死亡率的热二型真菌，如何逃避人类免疫系统。巨噬细胞极化成抑制真菌的M1样和促进真菌的M2样类型已被证明在针对真菌病原体的先天免疫应答中起重要作用。这种机制尚未被定义为T。马尔尼菲酒。在这里，我们证明了T. marneffei通过诱导它们朝向M2样极化来促进其在人巨噬细胞中的存活。我们的机制的调查表明，T。marneffei感染通过诱导酪氨酸磷酸化导致SOCS 3蛋白降解，从而减轻SOCS 3对p-STAT 6的抑制作用，p-STAT 6是M2样极化的关键因子。我们的SOCS 3过表达实验表明，SOCS 3是M1样极化的正调控因子，并在限制M2样极化中起重要作用。此外，我们发现TLR 9通路的抑制部分阻断了T。marneffei诱导的M2样极化显著增强巨噬细胞对T.马尔尼菲酒。总的来说，这些结果揭示了一种新的机制，T。马尔尼菲逃避了人类巨噬细胞的免疫反应。
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.
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