RRC ID 76109
Author Zheng Z, Zhang X, Liu J, He P, Zhang S, Zhang Y, Gao J, Yang S, Kang N, Afridi MI, Gao S, Chen C, Tu H.
Title GABAergic synapses suppress intestinal innate immunity via insulin signaling in Caenorhabditis elegans.
Journal Proc Natl Acad Sci U S A
Abstract 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.
Volume 118(20)
Published 2021-5-18
DOI 10.1073/pnas.2021063118
PII 2021063118
PMID 33972423
PMC PMC8157918
MeSH Adult Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / immunology* Caenorhabditis elegans / microbiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / immunology* Caenorhabditis elegans Proteins / physiology GABAergic Neurons / immunology GABAergic Neurons / metabolism GABAergic Neurons / microbiology Host-Pathogen Interactions / immunology Humans Immunity, Innate / genetics Immunity, Innate / immunology* Insulin / immunology* Insulin / metabolism Intestines / immunology* Intestines / microbiology Intestines / physiology Mutation Neuromuscular Junction / immunology Neuromuscular Junction / microbiology Neuromuscular Junction / physiology Pseudomonas aeruginosa / immunology Pseudomonas aeruginosa / physiology Receptors, GABA-A / genetics Receptors, GABA-A / immunology* Receptors, GABA-A / physiology Signal Transduction / immunology Synapses / immunology* Synapses / microbiology Synapses / physiology Synaptic Transmission / genetics Synaptic Transmission / immunology Synaptic Transmission / physiology
C.elegans tm1406 tm1165