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Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis

by Xu, Xingshun , Xin, Ning , Yuan, Yukang , Sun, Miao , Zuo, Yibo , Wang, Jun , Ren, Tengfei , Wang, Bin , Ruan, Hang , Liu, Xuan , Chen, Xiangjie , Miao, Ying , Guo, Tingting , Wu, Qiuyu , Zheng, Hui , Li, Shifeng , Wang, Junjie , Zhang, Hong-Guang , Yang, Yong , Dong, Chunsheng

in 13/21 / 13/31 / 14/35 / 38/109 / 38/56 / 38/91 / 59 / 631/250/262 / 631/80/458/582 / 631/80/86 / 64/60 / 82 / 82/1 / 82/58 / 82/79 / 82/80 / 96/95 / Adaptor Proteins, Vesicular Transport / Analgesics / Animal models / Animals / Antiviral drugs / Arginine Vasopressin / Argipressin / Biomedical and Life Sciences / Cell Biology / Depression - metabolism / Depressive Disorder, Major / Immune response / Immune system / Immunity / Immunity, Innate / Innate immunity / Interferon / Interferons / Leukocytes, Mononuclear / Life Sciences / Macrophages / Mental depression / Meptazinol / Mice / Patients / Peripheral blood mononuclear cells / Public health / Reduction / Signaling / Tyk2 protein / Vasopressin

2022

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2022

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2022

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Journal Article

Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis

Xu, Xingshun,

Xin, Ning,

Yuan, Yukang,

Sun, Miao,

Zuo, Yibo,

Wang, Jun,

Ren, Tengfei,

Wang, Bin,

Ruan, Hang,

Liu, Xuan,

Chen, Xiangjie,

Miao, Ying,

Guo, Tingting,

Wu, Qiuyu,

Zheng, Hui,

Li, Shifeng,

Wang, Junjie,

Zhang, Hong-Guang,

Yang, Yong,

Dong, Chunsheng

2022

Overview

Depression is a serious public-health issue. Recent reports have suggested higher susceptibility to viral infections in depressive patients. However, how depression affects antiviral innate immune signaling remains unknown. Here, we revealed a reduction in expression of Abelson helper integration site 1 (AHI1) in the peripheral blood mononuclear cells (PBMCs) and macrophages from the patients with major depressive disorder (MDD), which leads to attenuated antiviral immune response. We found that depression-related arginine vasopressin (AVP) induces reduction of AHI1 in macrophages. Further studies demonstrated that AHI1 is a critical stabilizer of basal type-I-interferon (IFN-I) signaling. Mechanistically, AHI1 recruits OTUD1 to deubiquitinate and stabilize Tyk2, while AHI1 reduction downregulates Tyk2 and IFN-I signaling activity in macrophages from both MDD patients and depression model mice. Interestingly, we identified a clinical analgesic meptazinol that effectively stimulates AHI1 expression, thus enhancing IFN-I antiviral defense in depression model mice. Our study promotes the understanding of the signaling mechanisms of depression-mediated antiviral immune dysfunction, and reveals meptazinol as an enhancer of antiviral innate immunity in depressive patients.

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Publisher

Springer Nature Singapore,Nature Publishing Group

Subject

13/21

/ 13/31

/ 14/35

/ 38/109

/ 38/56

/ 38/91

/ 59