| Synapse is the structure of information exchange between neurons and the basis of normal regulation of the nervous system.Innate immune system is the first line of defense against early infection and pathogen infection.Although the adaptive immune system has the function of "memory",which enables the host to resist the second infection of the same pathogen more accurately and effectively,the adaptive immune system is slow to respond to the new pathogen.Even in vertebrates,innate immunity is the basis of adaptive immunity and plays an important role in maintaining homeostasis.Compared with mammalian nervous system,c aenorhabditis elegans nervous system is simple but well structured,and only has a conserved innate immune system.In this study,the common human opportunistic pathogen PA14 was used to infect c.elegans,and it was found that the immunity of c.elegans w as enhanced after the mutation of the presynaptic transcription factor unc-30 related to GABA’s synaptic function,but decreased after the mutation of the unc-25 gene that controls the synthesis of GABA,while the immune-enhanced phenotype was consistent with that of the unc-30 gene after the mutation of the GABA postsynaptic receptor unc-49.It has been reported that deficiency of ingestion and excretion is an important factor affecting the survival rate of nematodes in intestinal pathogenic bacteria,which may also be the reason why unc-25 mutants among the three mutants only have excretion defect,so they are more sensitive to PA14 infection.Therefore,we saved the excretion defect of the unc-25 mutant and enhanced its immunity by specifically expressing t he promoter of GABA neurons in the head and tail to save its GABA synthesis.At the same time,we observed the instantaneous pharyngeal feeding amount and CFU experiment after pa14-gfp feeding unc-49 mutant and WT,excluding the influence of feeding amount,and preliminarily determined that d-type GABA synapse could inhibit nematode immunity.Then,in order to further understand type D GABA synaptic signaling pathway by which the immune to regulate innate immunity,we will be the classic control life and immune daf-2 / daf-16 gene deletion mutant hybrid to unc-49 mutant,found find daf-2 / daf-16 can affect unc-49 mutants in PA14 immunity,quantitative PCR and fluorescence imaging and display unc-49 after mutation daf-16 downstream increased immune gene expression.This suggests that GABA synapses regulate innate immunity of nematode worms through daf-2 / daf-16.In order to explore more information,we finally found that the expression of ins-31 was down-regulated in the infected unc-49 mutant through transcriptome sequencing,and ins-31 may be located downstream of unc-49 to inhibit innate immunity of nematode.We then verified this conclusion with RNAi and specific rescue experiments.Because ins-31 is an insulinlike factor,it may be located in the same signaling pathway as daf-2 / daf-16.Therefore,we finally concluded that nematode GABA could regulate innate immunity through the ins-31 pathway.This study will help to understand the functions of GABAergic synapses,GABAergic nervous systems,and innate immune systems in mammals and nematodes,and provide information for subsequent basic research.It also provides information for the understanding and treatment of the diseases relate to human innate immune system and nervous system... |
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