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S-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogens

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Listed:
  • Mutian Jia

    (Shandong University
    Shandong University)

  • Li Chai

    (Shandong University
    Shandong University)

  • Jie Wang

    (Shandong University
    Shandong University)

  • Mengge Wang

    (Shandong University
    Shandong University)

  • Danhui Qin

    (Shandong University
    Shandong University)

  • Hui Song

    (Shandong University
    Shandong University)

  • Yue Fu

    (Shandong University
    Shandong University)

  • Chunyuan Zhao

    (Shandong University)

  • Chengjiang Gao

    (Shandong University
    Shandong University)

  • Jihui Jia

    (Shandong University)

  • Wei Zhao

    (Shandong University
    Shandong University)

Abstract

Oxidative (or respiratory) burst confers host defense against pathogens by generating reactive species, including reactive nitrogen species (RNS). The microbial infection-induced excessive RNS damages many biological molecules via S-nitrosothiol (SNO) accumulation. However, the mechanism by which the host enables innate immunity activation during oxidative burst remains largely unknown. Here, we demonstrate that S-nitrosoglutathione (GSNO), the main endogenous SNO, attenuates innate immune responses against herpes simplex virus-1 (HSV-1) and Listeria monocytogenes infections. Mechanistically, GSNO induces the S-nitrosylation of stimulator of interferon genes (STING) at Cys257, inhibiting its binding to the second messenger cyclic guanosine monophosphate-adenosine monophosphate (cGAMP). Alcohol dehydrogenase 5 (ADH5), the key enzyme that metabolizes GSNO to decrease cellular SNOs, facilitates STING activation by inhibiting S-nitrosylation. Concordantly, Adh5 deficiency show defective STING-dependent immune responses upon microbial challenge and facilitates viral replication. Thus, cellular oxidative burst-induced RNS attenuates the STING-mediated innate immune responses to microbial infection, while ADH5 licenses STING activation by maintaining cellular SNO homeostasis.

Suggested Citation

  • Mutian Jia & Li Chai & Jie Wang & Mengge Wang & Danhui Qin & Hui Song & Yue Fu & Chunyuan Zhao & Chengjiang Gao & Jihui Jia & Wei Zhao, 2024. "S-nitrosothiol homeostasis maintained by ADH5 facilitates STING-dependent host defense against pathogens," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46212-z
    DOI: 10.1038/s41467-024-46212-z
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    1. Gabriele G. Schiattarella & Francisco Altamirano & Dan Tong & Kristin M. French & Elisa Villalobos & Soo Young Kim & Xiang Luo & Nan Jiang & Herman I. May & Zhao V. Wang & Theodore M. Hill & Pradeep P, 2019. "Nitrosative stress drives heart failure with preserved ejection fraction," Nature, Nature, vol. 568(7752), pages 351-356, April.
    2. Limin Liu & Alfred Hausladen & Ming Zeng & Loretta Que & Joseph Heitman & Jonathan S. Stamler, 2001. "A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans," Nature, Nature, vol. 410(6827), pages 490-494, March.
    3. Simone M. Haag & Muhammet F. Gulen & Luc Reymond & Antoine Gibelin & Laurence Abrami & Alexiane Decout & Michael Heymann & F. Gisou van der Goot & Gerardo Turcatti & Rayk Behrendt & Andrea Ablasser, 2018. "Targeting STING with covalent small-molecule inhibitors," Nature, Nature, vol. 559(7713), pages 269-273, July.
    4. Hiroki Ishikawa & Glen N. Barber, 2008. "Erratum: STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling," Nature, Nature, vol. 456(7219), pages 274-274, November.
    5. Hiroki Ishikawa & Glen N. Barber, 2008. "STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling," Nature, Nature, vol. 455(7213), pages 674-678, October.
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