PDF(Pubmed)
Abstract：
Newly weaned animals are susceptible to a wide range of microbial infections taking a high risk of developing post-weaning diarrhea. Trained immunity is the capacity of the innate immune system to produce a stronger and non-specific response against a secondary infection after the inflammatory response caused by previous stimulus has returned to normal state. The objective of this study was to evaluate if the heat-inactivated Escherichia coli (IEC) as an immunostimulant on suckling pups elicits a protective effect on the intestine of post-weaning rats challenged with Salmonella Typhimurium (S.Typhimurium). We adapted a newborn rat model for this purpose.
Sixty newborn pups were randomly separated into two groups: IEC group (n =30) orally administrated IEC during suckling, while the CON group received orally the same dose of saline. Both of the two group challenged with various doses of S.Typhimurium after experiencing a 4-week resting period. Twelve of individuals were selected to detect the survival rate, and ten of the rest were necropsied 48 hours post-challenge.
The results showed that oral administration of IEC during suckling alleviated the injury in ileal morphology induced by post-weaning S.Typhimurium infection via increasing the levels of two tight junction proteins [zonula occluden-1 (ZO-1) and Occludin-1] and several secreted proteins (Lysozyme, Mucin-2, and SIgA) in the intestinal mucosa. Furthermore, the pre-stimulation with IEC significantly increased cytokines tumor necrosis factor-alpha (TNF- α) and interleukin-1 beta (IL-1 β) expressions in an enhanced secondary reaction way after experiencing a 4-week resting period. This implicated the possible involvement of trained immunity. The 16S rDNA sequence results showed that pre-stimulation with IEC decreased the abundance of Clostridia, Prevotella, Christensenellaceae_R-7_group and Parabacteroides after intestinal infection of S.Typhimurium. Our results confirmed that the previous oral administration of IEC had a protective effect on S.Typhimurium-induced intestinal injury in weaned rats by inducing a robust immune response. The present study suggested a new strategy for preventing intestinal infection of newborn animals.
Sixty newborn pups were randomly separated into two groups: IEC group (n =30) orally administrated IEC during suckling, while the CON group received orally the same dose of saline. Both of the two group challenged with various doses of S.Typhimurium after experiencing a 4-week resting period. Twelve of individuals were selected to detect the survival rate, and ten of the rest were necropsied 48 hours post-challenge.
The results showed that oral administration of IEC during suckling alleviated the injury in ileal morphology induced by post-weaning S.Typhimurium infection via increasing the levels of two tight junction proteins [zonula occluden-1 (ZO-1) and Occludin-1] and several secreted proteins (Lysozyme, Mucin-2, and SIgA) in the intestinal mucosa. Furthermore, the pre-stimulation with IEC significantly increased cytokines tumor necrosis factor-alpha (TNF- α) and interleukin-1 beta (IL-1 β) expressions in an enhanced secondary reaction way after experiencing a 4-week resting period. This implicated the possible involvement of trained immunity. The 16S rDNA sequence results showed that pre-stimulation with IEC decreased the abundance of Clostridia, Prevotella, Christensenellaceae_R-7_group and Parabacteroides after intestinal infection of S.Typhimurium. Our results confirmed that the previous oral administration of IEC had a protective effect on S.Typhimurium-induced intestinal injury in weaned rats by inducing a robust immune response. The present study suggested a new strategy for preventing intestinal infection of newborn animals.
摘要：
■新断奶的动物容易受到广泛的微生物感染，具有发生断奶后腹泻的高风险。经过训练的免疫是先天性免疫系统在由先前刺激引起的炎症反应恢复到正常状态后产生针对继发感染的更强且非特异性反应的能力。这项研究的目的是评估热灭活的大肠杆菌（IEC）作为乳鼠幼犬的免疫刺激剂是否对受鼠伤寒沙门氏菌攻击的断奶后大鼠的肠道具有保护作用（S.鼠伤寒）。为此，我们采用了新生大鼠模型。
■将60只新生幼崽随机分为两组：IEC组（n=30）在哺乳期间口服IEC，CON组口服相同剂量的生理盐水。在经历了4周的休息期后，两组都用各种剂量的鼠伤寒沙门氏菌进行了攻击。选择12个人来检测存活率，其余10人在攻击后48小时进行尸检。
■结果表明，在哺乳期间口服IEC可以通过增加两种紧密连接蛋白[zonulaoccluden-1（ZO-1）和Occludin-1]和几种分泌蛋白（溶菌酶，肠粘膜中的粘蛋白2和SIgA）。此外，在经历了4周的静息期后，IEC的预刺激以增强的次级反应方式显着增加了细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的表达。这暗示了受过训练的免疫力的可能参与。16SrDNA序列结果表明，IEC预刺激降低了梭菌的丰度，普雷沃氏菌,伤寒沙门氏菌肠道感染后的Christensenellaceae_R-7_群和副杆菌属。我们的结果证实，先前口服IEC通过诱导强大的免疫反应对鼠伤寒沙门氏菌引起的断奶大鼠肠损伤具有保护作用。本研究提出了一种预防新生动物肠道感染的新策略。
■将60只新生幼崽随机分为两组：IEC组（n=30）在哺乳期间口服IEC，CON组口服相同剂量的生理盐水。在经历了4周的休息期后，两组都用各种剂量的鼠伤寒沙门氏菌进行了攻击。选择12个人来检测存活率，其余10人在攻击后48小时进行尸检。
■结果表明，在哺乳期间口服IEC可以通过增加两种紧密连接蛋白[zonulaoccluden-1（ZO-1）和Occludin-1]和几种分泌蛋白（溶菌酶，肠粘膜中的粘蛋白2和SIgA）。此外，在经历了4周的静息期后，IEC的预刺激以增强的次级反应方式显着增加了细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的表达。这暗示了受过训练的免疫力的可能参与。16SrDNA序列结果表明，IEC预刺激降低了梭菌的丰度，普雷沃氏菌,伤寒沙门氏菌肠道感染后的Christensenellaceae_R-7_群和副杆菌属。我们的结果证实，先前口服IEC通过诱导强大的免疫反应对鼠伤寒沙门氏菌引起的断奶大鼠肠损伤具有保护作用。本研究提出了一种预防新生动物肠道感染的新策略。
