GABAergic synapses suppress intestinal innate immunity via insulin signaling in <i>Caenorhabditis elegans</i>.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33972423.
- Also identified by DOI 10.1073/pnas.2021063118 and PMC identifier 8157918.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
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 <i>Caenorhabditis elegans</i> 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 GABA<sub>A</sub>R-deficient <i>unc-49</i> mutant compared with wild-type animals. <i>C. elegans</i> with <i>ins-31</i> knockdown or loss of function exhibited enhanced resistance to <i>Pseudomonas aeruginosa</i> 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.
Medical subject headings
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- Immunity, Innate
- Insulin
- Intestines
- Receptors, GABA-A
- Synapses