开菲尔水对 Toll 样受体 3 介导的肠道免疫反应的调节作用

Stefania Dentice Maidana, Ramiro Ortiz Moyano, M. Elean, Yoshiya Imamura, L. Albarracín, Fu Namai, Y. Suda, Keita Nishiyama, J. Villena, Haruki Kitazawa
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引用次数: 0

摘要

开菲尔对宿主的健康有益。以前研究开菲尔对免疫系统影响的工作主要集中在牛奶开菲尔或从牛奶开菲尔中提取的外多糖和细菌菌株上,而水开菲尔尚未进行评估。此外,研究主要集中在开菲尔调节免疫系统止血和发挥抗炎作用的能力上,而其对抗病毒免疫的具体作用还没有进行调查。因此,本研究旨在探讨开菲尔对由 Toll 样受体-3(TLR3)介导的肠道先天性抗病毒免疫的潜在免疫调节作用。成年 BALB/c 小鼠在饮用水中以 1:5、1:10 或 1:20 的比例稀释开菲尔水,连续喂食 6 天。第 7 天,处理组和未处理的对照组小鼠腹腔注射 TLR3 激动剂 poly(I:C)。TLR3 激活两天后,研究了肠道损伤和先天性免疫反应。腹腔注射聚(I:C)诱导了炎症介导的肠组织损伤,其特征是干扰素(IFNs)、促炎介质(TNF-α、IL-15、IL-6)和参与上皮破坏的因子(RAE-1和NKG2D)的上调。小肠样本的组织学分析表明,接受 1:5 开菲尔水治疗的小鼠水肿减轻,炎症细胞浸润减少。经过开菲尔处理的小鼠血清 LDH、AST 和 ALT 水平以及肠道 TNF-α、IL-15、IL-6、RAE-1 和 NKG2D 水平均显著降低。该组的肠道 IFN-β、IFN-γ 和 IL-10 浓度也较高。与对照组小鼠相比,1:10 的开菲尔水能减少肠道损伤和调节细胞因子,但其效果明显低于 1:5 的处理,而 1:20 的开菲尔水没有改变评估参数。结果表明,水酸乳以剂量依赖的方式发挥免疫调节作用。通过体内研究,我们可以推测开菲尔水能对肠道 TLR3 介导的免疫反应产生两种有益的影响:增强抗病毒防御能力和防止炎症介导的组织损伤。水酸乳的这些保护作用需要进一步探索,以了解水酸乳或其特定分子/菌株如何影响免疫反应,并确定其对真正病毒挑战的保护程度。
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Modulation of the Toll-like Receptor 3-Mediated Intestinal Immune Response by Water Kefir
Kefir has been associated with beneficial effects on its host’s health. The previous works examining the impact of kefir on the immune system focused on milk kefir or the exopolysaccharides and bacterial strains derived from it, while water kefir has not been evaluated. Furthermore, studies have focused on kefir’s ability to modulate immune system hemostasis and exert anti-inflammatory effects, while its specific action on antiviral immunity has not been investigated. Thus, the aim of this work was to examine the potential immunomodulatory effects of water kefir on the intestinal innate antiviral immunity mediated by Toll-like receptor-3 (TLR3). Adult BALB/c mice fed water kefir ad libitum, diluted 1:5, 1:10, or 1:20 in the drinking water, for 6 consecutive days. On day 7, the treated groups and the untreated control mice received an intraperitoneal injection of the TLR3 agonist poly(I:C). Two days after the TLR3 activation, the intestinal damage and the innate immune response were studied. The intraperitoneal administration of poly(I:C) induced inflammatory-mediated intestinal tissue damage, characterized by the upregulation of interferons (IFNs), pro-inflammatory mediators (TNF-α, IL-15, IL-6), and factors involved in epithelial destruction (RAE-1 and NKG2D). The histological analysis of small intestinal samples showed that mice receiving water kefir 1:5 exhibited reduced edema and a lower inflammatory cell infiltration. Kefir-treated mice had significantly lower levels of serum LDH, AST, and ALT as well as intestinal TNF-α, IL-15, IL-6, RAE-1, and NKG2D. This group also showed higher concentrations of intestinal IFN-β, IFN-γ, and IL-10. The treatment with 1:10 of water kefir reduced intestinal damage and modulated cytokines but its effect was significantly lower than the 1:5 treatment, while the water kefir 1:20 did not modify the parameters evaluated compared to control mice. The results indicate that water kefir exerts its immunomodulatory effects in a dose-dependent manner. The in vivo studies allow us to speculate that water kefir can induce two beneficial effects on the intestinal TLR3-mediated immune response: the enhancement of antiviral defenses and the protection against the inflammatory-mediated tissue damage. These protective effects of water kefir require further exploration to understand how water kefir, or its specific molecules/strains, can influence the immune response and to determine the extent of its protection against a real viral challenge.
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