S-nitrosothiol Homeostasis Maintained by ADH5 Facilitates STING-dependent Host Defense Against Pathogens

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Feb 26

PMID 38409248

Authors

Mutian Jia

Li Chai

Jie Wang

Mengge Wang

Danhui Qin

Hui Song

Yue Fu

Chunyuan Zhao

Chengjiang Gao

Jihui Jia

Wei Zhao

Affiliations

Soon will be listed here.

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.

Citing Articles

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PMID: 39508503 PMC: 11562918. DOI: 10.1080/21505594.2024.2425744.

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