Elean M, Albarracín L, Cataldo P G, Londero A, Kitazawa H, Saavedra L, Villena J, Hebert E M
Reference Centre for Lactobacilli (CERELA-CONICET), Calle Batalla de Chacabuco 145, Tucuman, 4000, Argentina.
Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, 984-0051, Japan.
Benef Microbes. 2020 Aug 12;11(4):375-390. doi: 10.3920/BM2019.0198. Epub 2020 Aug 5.
Proteolytic starter cultures with intrinsic immunomodulatory activities are desirably features for the development of functional foods, which would significantly reduce the cost of their production (one-strain starter) having an additional beneficial effect on the host. In this work, strains were selected according to their ability to efficiently hydrolyse β-casein and to modulate the immune system. Among 36 strains evaluated, the highest proteolytic activities were found for subsp. CRL581 and subsp. CRL656. The immunomodulatory effect of both strains and their β-casein hydrolysates (CRL581 and CRL656 hydrolysates, respectively) were studied in a murine model. Balb/c mice were fed lactobacilli or their hydrolysates for three days. One day after the last lactobacilli or hydrolysate treatments, mice were challenged with the Toll-like receptor 3 (TLR3) agonist poly(I:C) by intraperitoneal injection. Before and after poly(I:C) challenge the phagocytic and microbicidal activity of peritoneal macrophages, intestinal immunoglobulin A (IgA), cytokine profile, and histological analysis of the intestine were analysed. subsp. CRL581 significantly increased the activation of peritoneal macrophages as well as the levels of intestinal IgA, interleukin (IL)-10 and interferon (IFN)-γ when compared to untreated controls. In addition, the CRL581 strain was able to significantly reduce the intestinal inflammatory damage triggered by TLR3 activation. CRL581 increased the levels of IL-10, IFN-γ and IFN-β, and reduced tumour necrosis factor alpha and IL-6 concentrations in the intestine of poly(I:C)-challenged mice. No immunomodulatory effects were observed for the CRL656 strain or for the CRL581 or CRL656 hydrolysates. The results of this work show that the technologically relevant and high proteolytic strain CRL581 is able to beneficially modulate the intestinal innate antiviral immune response. Although further studies with the CRL581 strain are required to corroborate and deepen its immunological effects, this bacterium is an interesting alternative for the development of new functional foods with antiviral capabilities.
具有内在免疫调节活性的蛋白水解发酵剂培养物是功能性食品开发的理想特性，这将显著降低其生产成本（单菌株发酵剂），并对宿主产生额外的有益影响。在这项工作中，根据菌株有效水解β-酪蛋白和调节免疫系统的能力进行选择。在评估的36株菌株中，发现嗜热栖热放线菌亚种CRL581和嗜热栖热放线菌亚种CRL656具有最高的蛋白水解活性。在小鼠模型中研究了这两种菌株及其β-酪蛋白水解产物（分别为CRL581和CRL656水解产物）的免疫调节作用。给Balb/c小鼠喂食乳酸杆菌或其水解产物三天。在最后一次乳酸杆菌或水解产物处理一天后，通过腹腔注射用Toll样受体3（TLR3）激动剂聚肌苷酸-聚胞苷酸（poly(I:C)）攻击小鼠。在poly(I:C)攻击前后，分析腹膜巨噬细胞的吞噬和杀菌活性、肠道免疫球蛋白A（IgA）、细胞因子谱以及肠道的组织学分析。与未处理的对照相比，嗜热栖热放线菌亚种CRL581显著增加了腹膜巨噬细胞的活化以及肠道IgA、白细胞介素（IL）-10和干扰素（IFN）-γ的水平。此外，CRL581菌株能够显著减轻由TLR3激活引发的肠道炎症损伤。CRL581增加了poly(I:C)攻击小鼠肠道中IL-10、IFN-γ和IFN-β的水平，并降低了肿瘤坏死因子α和IL-6的浓度。未观察到CRL656菌株或CRL581或CRL656水解产物的免疫调节作用。这项工作的结果表明，技术上相关且蛋白水解能力高的菌株CRL581能够有益地调节肠道先天性抗病毒免疫反应。尽管需要对CRL581菌株进行进一步研究以证实和深化其免疫效果，但这种细菌是开发具有抗病毒能力的新型功能性食品的一个有趣选择。
