Institute of Nutrition and Food Technology José Mataix, Biomedical Research Centre, Department of Biochemistry and Molecular Biology II, University of Granada, Granada, Spain.
PLoS One. 2012;7(8):e43197. doi: 10.1371/journal.pone.0043197. Epub 2012 Aug 14.
Probiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, little is known about the signalling pathways that are engaged by probiotics. Dendritic cells (DCs) are antigen-presenting cells that are involved in immunity and tolerance. Monocyte-derived dendritic cells (MoDCs) and murine DCs are different from human gut DCs; therefore, in this study, we used human DCs generated from CD34+ progenitor cells (hematopoietic stem cells) harvested from umbilical cord blood; those DCs exhibited surface antigens of dendritic Langerhans cells, similar to the lamina propria DCs in the gut. We report that both a novel probiotic strain isolated from faeces of exclusively breast-fed newborn infants, Lactobacillus paracasei CNCM I-4034, and its cell-free culture supernatant (CFS) decreased pro-inflammatory cytokines and chemokines in human intestinal DCs challenged with Salmonella. Interestingly, the supernatant was as effective as the bacteria in reducing pro-inflammatory cytokine expression. In contrast, the bacterium was a potent inducer of TGF-β2 secretion, whereas the supernatant increased the secretion of TGF-β1 in response to Salmonella. We also showed that both the bacteria and its supernatant enhanced innate immunity through the activation of Toll-like receptor (TLR) signalling. These treatments strongly induced the transcription of the TLR9 gene. In addition, upregulation of the CASP8 and TOLLIP genes was observed. This work demonstrates that L. paracasei CNCM I-4034 enhanced innate immune responses, as evidenced by the activation of TLR signalling and the downregulation of a broad array of pro-inflammatory cytokines. The use of supernatants like the one described in this paper could be an effective and safe alternative to using live bacteria in functional foods.
益生菌已被证明可调节免疫反应，并可能在过敏和炎症性疾病中具有治疗作用。然而，人们对益生菌所涉及的信号通路知之甚少。树突状细胞（DC）是参与免疫和耐受的抗原呈递细胞。单核细胞衍生的树突状细胞（MoDC）和鼠类 DC 与人类肠道 DC 不同；因此，在这项研究中，我们使用了从脐血中采集的 CD34+祖细胞（造血干细胞）生成的人 DC；这些 DC 表现出树突状朗格汉斯细胞的表面抗原，类似于肠道中的固有层 DC。我们报告说，一种从纯母乳喂养的新生儿粪便中分离出来的新型益生菌菌株，即副干酪乳杆菌 CNCM I-4034，及其无细胞培养上清液（CFS），可降低受沙门氏菌攻击的人肠道 DC 中的促炎细胞因子和趋化因子。有趣的是，上清液在降低促炎细胞因子表达方面与细菌一样有效。相比之下，该细菌是 TGF-β2 分泌的有效诱导剂，而上清液则增加了对沙门氏菌的 TGF-β1 分泌。我们还表明，细菌及其上清液均通过激活 Toll 样受体（TLR）信号来增强固有免疫。这些处理强烈诱导 TLR9 基因的转录。此外，还观察到 CASP8 和 TOLLIP 基因的上调。这项工作表明，副干酪乳杆菌 CNCM I-4034 通过激活 TLR 信号和下调广泛的促炎细胞因子来增强固有免疫反应。像本文中描述的那样使用上清液可能是在功能性食品中使用活菌的有效且安全的替代方法。
