PDF(Pubmed)
Abstract：
The gut microbiota is a complex group of microorganisms that is not only closely related to intestinal immunity but also affects the whole immune system of the body. Antimicrobial peptides and reactive oxygen species participate in the regulation of gut microbiota homeostasis in invertebrates. However, it is unclear whether nitric oxide, as a key mediator of immunity that plays important roles in antipathogen activity and immune regulation, participates in the regulation of gut microbiota homeostasis. In this study, we identified a nitric oxide synthase responsible for NO production in the shrimp Marsupenaeus japonicus. The expression of Nos and the NO concentration in the gastrointestinal tract were increased significantly in shrimp orally infected with Vibrio anguillarum. After RNA interference of Nos or treatment with an inhibitor of NOS, L-NMMA, NO production decreased and the gut bacterial load increased significantly in shrimp. Treatment with the NO donor, sodium nitroprusside, increased the NO level and reduced the bacterial load significantly in the shrimp gastrointestinal tract. Mechanistically, V. anguillarum infection increased NO level via upregulation of NOS and induced phosphorylation of ERK. The activated ERK phosphorylated the NF-κB-like transcription factor, dorsal, and caused nuclear translocation of dorsal to increase expression of antimicrobial peptides (AMPs) responsible for bacterial clearance. In summary, as a signaling molecule, NOS-produced NO regulates intestinal microbiota homeostasis by promoting AMP expression against infected pathogens via the ERK-dorsal pathway in shrimp.
摘要：
肠道菌群是一类复杂的微生物群，不仅与肠道免疫密切相关，而且影响机体的整个免疫系统。抗菌肽和活性氧参与无脊椎动物肠道菌群稳态的调节。然而,目前还不清楚一氧化氮，作为免疫的关键介质，在抗病原体活性和免疫调节中起重要作用，参与肠道菌群稳态的调节。在这项研究中,我们确定了负责日本对虾中NO产生的一氧化氮合酶。经口感染的鳗鱼弧菌对虾中Nos的表达和胃肠道中NO的浓度显着增加。RNA干扰Nos或用NOS抑制剂处理后，L-NMMA,虾中NO的产生减少，肠道细菌负荷显着增加。用NO供体治疗，硝普钠,显著提高了虾胃肠道的NO水平，降低了细菌负荷。机械上,V.anguillarum感染通过上调NOS和诱导ERK磷酸化来增加NO水平。活化的ERK磷酸化NF-κB样转录因子，背侧,并导致背侧核易位，以增加负责细菌清除的抗菌肽（AMPs）的表达。总之,作为信号分子，NOS产生的NO通过在虾中通过ERK-背侧途径促进针对感染病原体的AMP表达来调节肠道微生物群的稳态。
