Abstract
The neuroendocrine-immune (NEI) regulatory network is a complex system, which plays an indispensable role in the immunity of the host. In the present study, the bioinformatical analysis of the transcriptomic data from oyster Crassostrea gigas and further biological validation revealed that oyster TNF (CgTNF-1 CGI_10018786) could activate the transcription factors NF-κB and HSF (heat shock transcription factor) through MAPK signaling pathway, and then regulate apoptosis, redox reaction, neuro-regulation and protein folding in oyster haemocytes. The activated immune cells then released neurotransmitters including acetylcholine, norepinephrine and [Met5]-enkephalin to regulate the immune response by arising the expression of three TNF (CGI_10005109, CGI_10005110 and CGI_10006440) and translocating two NF-κB (Cgp65, CGI_10018142 and CgRel, CGI_10021567) between the cytoplasm and nuclei of haemocytes. Neurotransmitters exhibited the immunomodulation effects by influencing apoptosis and phagocytosis of oyster haemocytes. Acetylcholine and norepinephrine could down-regulate the immune response, while [Met5]-enkephalin up-regulate the immune response. These results suggested that the simple neuroendocrine-immune regulatory network in oyster might be activated by oyster TNF and then regulate the immune response by virtue of neurotransmitters, cytokines and transcription factors.
Highlights
Homeostasis[4,5,6]
For the internal connectivity among the 14 genes, 4 genes (CGI_10005110: tumor necrosis factor ligand superfamily number 14, CGI_10017654: NF-kappa-B inhibitor epsilon, CGI_10018951: AP-1 complex subunit gamma-1 and CGI_10024309: heat shock protein 75 kDa) in the yellow module and 5 genes (CGI_10006440: tumor necrosis factor ligand superfamily member 11, CGI_10005825: tripeptidyl-peptidase 2, CGI_100023787: AP-2 complex subunit beta, CGI_10023156: TNF receptor-associated factor 3 and CGI_10027979: TNF receptor-associated factor 6) in the turquoise module formed a network with TNF (CGI_10006440) as the hubgene (Fig. 5B)
In the present transcriptome analysis, the NEI system in oyster could be quickly activated by tumor necrosis factor (CgTNF-1)
Summary
Homeostasis[4,5,6]. There are various kinds of neuroendocrine-immune axes and neuroendocrine cells in mammals to impinge on neuro-immunomodulation[4]. Catecholaminergic and cholinergic system, [Met5]-enkephalin and its receptor, as well as cytokines such as tumor necrosis factor (TNF) were reported to be existed in scallop C. farreri[19,20,21] and oyster C. gigas[22,23], which opened up new horizons and provided us an entrance to a better understanding of the neuroendocrine-immune regulatory network in invertebrates. The purposes of this study are to (1) identify the molecular components of NEI regulatory network in oyster C. gigas, (2) explore the potential activation mechanism of neuroendocrine system, (3) investigate the immunomodulation of neurotransmitter acetylcholine, norepinephrine and [Met5]-enkephalin, and (4) evaluate the synergic effects of neurotransmitters on oyster immune system
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