GABAergic synapses suppress intestinal innate immunity via insulin signaling in Caenorhabditis elegans

Autor:	Chunhong Chen, Na Kang, Xiumei Zhang, Zhongfan Zheng, Junqiang Liu, Shan Zhang, Yongning Zhang, Ping He, Haijun Tu, Jie Gao, Shangbang Gao, Muhammad Irfan Afridi, Shengmei Yang
Rok vydání:	2021
Předmět:	Gene knockdown Insulin receptor Multidisciplinary Immune system Innate immune system biology biology.protein GABAergic Inhibitory postsynaptic potential biology.organism_classification Loss function Caenorhabditis elegans Cell biology
Zdroj:	Proceedings of the National Academy of Sciences. 118
ISSN:	1091-6490 0027-8424
Popis:	GABAergic neurotransmission constitutes a major inhibitory signaling mechanism that plays crucial roles in central nervous system physiology and immune cell immunomodulation. However, its roles in innate immunity remain unclear. Here, we report that deficiency in the GABAergic neuromuscular junctions (NMJs) of Caenorhabditis elegans results in enhanced resistance to pathogens, whereas pathogen infection enhances the strength of GABAergic transmission. GABAergic synapses control innate immunity in a manner dependent on the FOXO/DAF-16 but not the p38/PMK-1 pathway. Our data reveal that the insulin-like peptide INS-31 level was dramatically decreased in the GABAergic NMJ GABAAR-deficient unc-49 mutant compared with wild-type animals. C. elegans with ins-31 knockdown or loss of function exhibited enhanced resistance to Pseudomonas aeruginosa PA14 exposure. INS-31 may act downstream of GABAergic NMJs and in body wall muscle to control intestinal innate immunity in a cell-nonautonomous manner. Our results reveal a signaling axis of synapse–muscular insulin–intestinal innate immunity in vivo.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::02d2195cd20cc6aaa35dc1b2c92a0958 https://doi.org/10.1073/pnas.2021063118 Zobrazit plný text záznamu