Faculty of Life Sciences, Department of Basic Sciences and Environment, University of Copenhagen, Frederiksberg C, Denmark.
Immunology. 2010 Oct;131(2):268-81. doi: 10.1111/j.1365-2567.2010.03301.x.
Lactobacilli are probiotics that, among other health-promoting effects, have been ascribed immunostimulating and virus-preventive properties. Certain Lactobacillus spp. have been shown to possess strong interleukin-12 (IL-12) -inducing properties. As IL-12 production depends on the up-regulation of type I interferons (IFNs), we hypothesized that the strong IL-12-inducing capacity of Lactobacillus acidophilus NCFM in murine bone-marrow-derived dendritic cells (DCs) is caused by an up-regulation of IFN-β, which subsequently induces IL-12 and the double-stranded RNA binding Toll-like receptor-3 (TLR-3). The expression of the genes encoding IFN-β, TLR-3, IL-12 and IL-10 in DCs upon stimulation with L. acidophilus NCFM was determined. Lactobacillus acidophilus NCFM induced a much stronger expression of Ifn-β, Il-12 and Il-10 compared with the synthetic double-stranded RNA ligand Poly I:C, whereas the levels of expressed Tlr-3 were similar. Whole genome microarray gene expression analysis revealed that other genes related to viral defence were significantly up-regulated and among the strongest induced genes in DCs stimulated with L. acidophilus NCFM. The ability to induce IFN-β was also detected in another L. acidophilus strain (X37), but was not a property of other probiotic strains tested, i.e. Bifidobacterium bifidum Z9 and Escherichia coli Nissle 1917. The IFN-β expression was markedly reduced in TLR-2(-/-) DCs, dependent on endocytosis, and the major cause of the induction of Il-12 and Tlr-3 in DCs stimulated with L. acidophilus NCFM. Collectively, our results reveal that certain lactobacilli trigger the expression of viral defence genes in DCs in a TLR-2 manner dependent on IFN-β.
乳杆菌是益生菌，除了其他促进健康的作用外，还具有免疫刺激和预防病毒的特性。某些乳杆菌属已被证明具有很强的诱导白细胞介素-12（IL-12）的特性。由于 IL-12 的产生依赖于 I 型干扰素（IFN）的上调，我们假设嗜酸乳杆菌 NCFM 在鼠骨髓来源的树突状细胞（DC）中具有很强的诱导 IL-12 的能力是由于 IFN-β的上调，这随后诱导 IL-12 和双链 RNA 结合 Toll 样受体-3（TLR-3）。在刺激 DC 时，用乳杆菌 NCFM 刺激后 DC 中编码 IFN-β、TLR-3、IL-12 和 IL-10 的基因的表达。与合成双链 RNA 配体 Poly I:C 相比，嗜酸乳杆菌 NCFM 诱导 Ifn-β、Il-12 和 Il-10 的表达要强得多，而表达的 Tlr-3 水平相似。全基因组微阵列基因表达分析显示，与病毒防御相关的其他基因显著上调，并且在 DC 中受嗜酸乳杆菌 NCFM 刺激时最强诱导的基因之一。在另一种嗜酸乳杆菌（X37）中也检测到诱导 IFN-β 的能力，但不是测试的其他益生菌菌株的特性，即双歧杆菌双歧杆菌 Z9 和大肠杆菌 Nissle 1917。TLR-2（-/-）DC 中的 IFN-β 表达明显降低，依赖于内吞作用，并且是嗜酸乳杆菌 NCFM 刺激的 DC 中诱导 Il-12 和 Tlr-3 的主要原因。总之，我们的结果表明，某些乳杆菌以 TLR-2 方式依赖于 IFN-β触发 DC 中病毒防御基因的表达。
