Cholinergic Activation Enhances Resistance to Oral Salmonella Infection by Modulating Innate Immune Defense Mechanisms at the Intestinal Barrier.
Cholinergic Activation Enhances Resistance to Oral Salmonella Infection by Modulating Innate Immune Defense Mechanisms at the Intestinal Barrier.
复制标题
DOI：
10.3389/fimmu.2018.00551
复制
发表时间：
2018
影响因子：
7.3
通讯作者：
Fernandez-Cabezudo MJ
中科院分区：
文献类型：
--
作者：
Al-Barazie RM;Bashir GH;Qureshi MM;Mohamed YA;Al-Sbiei A;Tariq S;Lammers WJ;Al-Ramadi BK;Fernandez-Cabezudo MJ
炎症是一种重要的防御机制，可以保护身体免受入侵病原体的破坏性影响。然而，不受限制的炎症反应可能导致全身表现，对宿主造成可怕的后果。炎症反应的激活程度通过免疫和神经途径受到严格调节。以前，我们证明，胆碱能刺激赋予增强的保护，在实验动物口服感染的毒性沙门氏菌肠道血清型鼠伤寒。在这项研究中，我们研究了这种增强保护的机制。胆碱能刺激诱导3周的预处理与对氧磷，一种高度特异性的乙酰胆碱酯酶（AChE）抑制剂。这种治疗增强了口服途径感染后的宿主存活率，这与全身靶器官中细菌负荷的显著降低相关。增强的保护不是由于增加肠道蠕动或快速清除胃肠道细菌。此外，当动物全身感染时，对细菌感染的保护并不明显，这表明乙酰胆碱介导的保护作用主要限于肠道粘膜组织。在体内成像显示了一个更本地化的感染和延迟细菌传播到全身器官的小鼠预处理与对氧磷。小肠（回肠）的形态学分析表明，乙酰胆碱酯酶抑制诱导脱粒的杯状细胞和潘氏细胞，两个专门的分泌细胞参与先天免疫。我们的研究结果表明，神经和免疫系统之间的一个重要途径，在粘膜界面，以保护主机对口腔病原体。
Inflammation is a crucial defense mechanism that protects the body from the devastating effects of invading pathogens. However, an unrestrained inflammatory reaction may result in systemic manifestations with dire consequences to the host. The extent of activation of the inflammatory response is tightly regulated through immunological and neural pathways. Previously, we demonstrated that cholinergic stimulation confers enhanced protection in experimental animals orally infected with virulent Salmonella enterica serovar Typhimurium. In this study, we investigated the mechanism by which this enhanced protection takes place. Cholinergic stimulation was induced by a 3-week pretreatment with paraoxon, a highly specific acetylcholinesterase (AChE) inhibitor. This treatment enhanced host survival following oral-route infection and this correlated with significantly reduced bacterial load in systemic target organs. Enhanced protection was not due to increased gut motility or rapid bacterial clearance from the gastrointestinal tract. Moreover, protection against bacterial infection was not evident when the animals were infected systemically, suggesting that acetylcholine-mediated protective effect was mostly confined to the gut mucosal tissue. In vivo imaging demonstrated a more localized infection and delay in bacterial dissemination into systemic organs in mice pretreated with paraoxon. Morphological analysis of the small intestine (ileum) showed that AChE inhibition induced the degranulation of goblet cells and Paneth cells, two specialized secretory cells involved in innate immunity. Our findings demonstrate a crucial pathway between neural and immune systems that acts at the mucosal interface to protect the host against oral pathogens.
影响因子：
--
作者：
Pohanka M;Pavlis O;Svobodova H;Pikula J
通讯作者：
Pikula J