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Front. Immunol. | doi: 10.3389/fimmu.2018.00284

The cholinergic and adrenergic autocrine signaling pathway mediates immunomodulation in oyster Crassostrea gigas

Zhaoqun Liu1, 2, 3,  Lingling Wang1*, Zhao Lv3, 4, Zhi Zhou5,  Weilin Wang1,  Meijia Li3, 4, Qilin Yi1, Limei Qiu3 and  Linsheng Song1, 2*
  • 1Dalian Ocean University, China
  • 2Qingdao National Laboratory for Marine Science and Technology, China
  • 3Institute of Oceanology (CAS), China
  • 4University of Chinese Academy of Sciences (UCAS), China
  • 5Hainan University, China

It is becoming increasingly clear that neurotransmitters impose direct influence on regulation of the immune process. Recently, a simple but sophisticated neuroendocrine-immune (NEI) system was identified in oyster, which modulated neural immune response via a “nervous-hemocyte”-mediated neuroendocrine immunomodulatory axis (NIA)-like pathway. In the present study, the de novo synthesis of neurotransmitters and their immunomodulation in the hemocytes of oyster Crassostrea gigas were investigated to understand the autocrine/paracrine pathway independent of the nervous system in oyster. After hemocytes were exposed to lipopolysaccharide (LPS) stimulation, acetylcholine (ACh) and norepinephrine (NE) in the cell supernatants both increased to a significantly higher level (2.71- and 2.40-fold, p < 0.05) comparing with that in the control group. The mRNA expression levels and protein activities of choline O-acetyltransferase (CgChAT) and dopamine β-hydroxylase (CgDBH) in hemocytes which were involved in the synthesis of ACh and NE were significantly elevated at 1 h after LPS stimulation, while the activities of acetylcholinesterase (CgAChE) and monoamine oxidase (CgMAO), two enzymes essential in metabolic inactivation of ACh and NE, were inhibited. These results demonstrated the existence of the sophisticated intracellular machinery for the generation, release and inactivation of ACh and NE in oyster hemocytes. Moreover, the hemocyte-derived neurotransmitters could in turn regulate the mRNA expressions of tumor necrosis factor (TNF) genes, the activities of superoxide dismutase (SOD), catalase (CAT) and lysosome (LYZ), and hemocyte phagocytosis. The phagocytic activities of hemocytes, the mRNA expressions of TNF and the activities of key immune-related enzymes were significantly changed after the block of ACh and NE receptors with different kinds of antagonists, suggesting that autocrine/paracrine self-regulation was mediated by transmembrane receptors on hemocyte. The present study proved that oyster hemocyte could de novo synthesize and release cholinergic and adrenergic neurotransmitters, and the hemocyte-derived ACh/NE could then execute a negative regulation on hemocyte phagocytosis and synthesis of immune effectors with similar autocrine/paracrine signaling pathway identified in vertebrate macrophages. Findings in the present study demonstrated that the immune and neuroendocrine system evolved from a common origin and enriched our knowledge on the evolution of NEI system.

Keywords: Crassostrea gigas, Autocrine/paracrine, Haemocyte, neurotransmitter, membrane receptor, Immune Regulation

Received: 30 Nov 2017; Accepted: 31 Jan 2018.

Edited by:

Lluis Tort, Universitat Autònoma de Barcelona, Spain

Reviewed by:

Loriano Ballarin, Università degli Studi di Padova, Italy
Hai-peng Liu, Xiamen University, China  

Copyright: © 2018 Liu, Wang, Lv, Zhou, Wang, Li, Yi, Qiu and Song. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Lingling Wang, Dalian Ocean University, Dalian, China, wanglingling@dlou.edu.cn
Prof. Linsheng Song, Dalian Ocean University, Dalian, China, lshsong@dlou.edu.cn