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GABAergic Neuromuscular Junction Suppresses Intestinal Defense of Caenorhabditis elegans by Attenuating Muscular Oxidative Phosphorylation

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posted on 2022-11-28, 19:52 authored by Jiayu Wu, Shengmei Yang, Junqiang Liu, Zhongfan Zheng, Ming Lei, Pei Zhang, Lukas Stingelin, Jinjun Chen, Lizhi Xiong, Haijun Tu
Innate immunity is an ancient and evolutionarily conserved system that constitutes the first line of host defense against invading microbes. We previously determined that the GABAergic neuromuscular junction (NMJ) suppresses intestinal innate immunity via muscular insulin signaling. Here, we found that a muscular mitochondrial oxidative phosphorylation pathway of Caenorhabditis elegans is involved in GABAergic NMJs-mediated intestinal defense. Deficiency in GABAergic neurotransmission increases reactive oxygen species (ROS) abundance and inhibits the nuclear translocation of SKN-1, whereas exogenous GABA administration represses it. SKN-1 is an important transcription factor involved in oxidative stress and the innate immune response. Moreover, deficiency in GABAergic postsynaptic UNC-49/GABAAR robustly promotes the mitochondrial function of GABAergic postsynaptic muscle cells, which may contribute to the muscular ROS decrease and intestinal SKN-1 suppression, ultimately inhibiting the intestinal defense of C. elegans. Our findings reveal a potential role of muscle mitochondrial ROS in intestinal defense in vivo and expand our understanding of mechanisms of intestinal innate immunity.

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