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Manganese (II) Activates cGAS-STING pathway

ABSTRACT: We show that Manganese (II) is a potent type I-IFN inducing agonist, stimulating cells into an anti-viral state in the absence of infection. Mechanically, Mn2+ treatment led to a profound cGAS-STING-dependent innate immune activation, conferring cells or mice viral resistance. Overall design: THP1 cells were treated with Mn2+, VACV, IFNβ or empty media (control). RNA was extracted and sequenced.

INSTRUMENT(S): Illumina HiSeq 2500 (Homo sapiens)

SUBMITTER: Yukun Guan  

PROVIDER: GSE77216 | GEO | 2018-10-09


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Manganese Increases the Sensitivity of the cGAS-STING Pathway for Double-Stranded DNA and Is Required for the Host Defense against DNA Viruses.

Wang Chenguang C   Guan Yukun Y   Lv Mengze M   Zhang Rui R   Guo Zhaoying Z   Wei Xiaoming X   Du Xiaoxia X   Yang Jing J   Li Tong T   Wan Yi Y   Su Xiaodong X   Huang Xiaojun X   Jiang Zhengfan Z  

Immunity 20180410 4

Manganese (Mn) is essential for many physiological processes, but its functions in innate immunity remain undefined. Here, we found that Mn<sup>2+</sup> was required for the host defense against DNA viruses by increasing the sensitivity of the DNA sensor cGAS and its downstream adaptor protein STING. Mn<sup>2+</sup> was released from membrane-enclosed organelles upon viral infection and accumulated in the cytosol where it bound directly to cGAS. Mn<sup>2+</sup> enhanced the sensitivity of cGAS t  ...[more]

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