| RRC ID |
80818
|
| Author |
Liu J, Zhang P, Zheng Z, Afridi MI, Zhang S, Wan Z, Zhang X, Stingelin L, Wang Y, Tu H.
|
| Title |
GABAergic signaling between enteric neurons and intestinal smooth muscle promotes innate immunity and gut defense in Caenorhabditis elegans.
|
| Journal |
Immunity
|
| Abstract |
The nervous system is critical for intestinal homeostasis and function, but questions remain regarding its impact on gut immune defense. By screening the major neurotransmitters of C. elegans, we found that γ-aminobutyric acid (GABA) deficiency enhanced susceptibility to pathogenic Pseudomonas aeruginosa PA14 infection. GABAergic signaling between enteric neurons and intestinal smooth muscle promoted gut defense in a PMK-1/p38-dependent, but IIS/DAF-16- and DBL-1/TGF-β-independent, pathway. Transcriptomic profiling revealed that the neuropeptide, FLP-6, acted downstream of enteric GABAergic signaling. Further data determined that FLP-6 was expressed and secreted by intestinal smooth muscle cells and functioned as a paracrine molecule on the intestinal epithelium. FLP-6 suppressed the transcription factors ZIP-10 and KLF-1 that worked in parallel and converged to the PMK-1/p38 pathway in the intestinal epithelia for innate immunity and gut defense. Collectively, these findings uncover an enteric neuron-muscle-epithelium axis that may be evolutionarily conserved in higher organisms.
|
| Volume |
56(7)
|
| Pages |
1515-1532.e9
|
| Published |
2023-7-11
|
| DOI |
10.1016/j.immuni.2023.06.004
|
| PII |
S1074-7613(23)00261-3
|
| PMID |
37437538
|
| MeSH |
Animals
Caenorhabditis elegans*
Immunity, Innate
Muscle, Smooth
Neurons*
Signal Transduction
|
| Resource |
| C.elegans |
tm1406
tm1165
tm4085
tm5156
tm2105
tm1712 |
