Lactobacilli differentially modulate expression of cytokines and maturation surface markers in murine dendritic cells
Lactobacilli differentially modulate expression of cytokines and maturation surface markers in murine dendritic cells
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DOI：
10.4049/jimmunol.168.1.171
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发表时间：
2002-01-01
影响因子：
4.4
通讯作者：
Pestka, JJ
中科院分区：
文献类型：
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作者：
Christensen, HR;Frokiær, H;Pestka, JJ
树突状细胞（DC）在Th1、Th2和Th3细胞平衡中起着关键的免疫调节作用，存在于整个胃肠道中。因此，DC可能是肠道微生物（包括摄入的益生菌）调节的靶点。在本研究中，我们验证了一种假设，即肠道菌群的重要成员乳酸杆菌，可以不同地激活DC。将骨髓来源的小鼠DC暴露于各种致命辐射的乳酸杆菌中，并分析由此产生的培养上清中IL-6、IL-10、IL-12和tnf - α的含量。不同菌株诱导DC细胞产生IL-12和TNF-a的能力存在显著差异。在诱导IL-6和IL-10方面，乳酸菌之间存在类似但不太明显的差异。虽然所有菌株都上调了表面MHC II类和B7-2 (CD86)，这表明DC成熟，但诱导IL-12能力最强的乳酸菌效果最好。值得注意的是，弱诱导IL-12的罗伊氏乳杆菌（Lactobacillus reuteri） DSM12246抑制了强诱导IL-12、IL-6和tnf - α的诱导作用，而IL-10的产生保持不变。以类似的方式，罗伊氏乳杆菌减少了L casei诱导的B7-2上调。这些结果表明，不同种类的乳酸菌具有非常不同的DC激活模式，而且，至少有一种乳酸菌可能能够抑制该属其他物种的活性。因此，肠道DC的Th1/Th2/ th3驱动能力可能会根据肠道菌群的组成（包括摄入的益生菌）进行调节。
Dendritic cells (DC) play a pivotal immunoregulatory role in the Th1, Th2, and Th3 cell balance and are present throughout the gastrointestinal tract. Thus, DC may be targets for modulation by gut microbes, including ingested probiotics. In the present study, we tested the hypothesis that species of Lactobacillus, important members of the gut flora, differentially activate DC. Bone marrow-derived murine DC were exposed to various lethally irradiated Lactobacillus spp. and resultant culture supernatants were analyzed for IL-6, IL-10, IL-12, and TNF-alpha. Substantial differences were found among strains in the capacity to induce IL-12 and TNF-a production in the DC. Similar but less pronounced differences were observed among lactobacilli in the induction of IL-6 and IL-10. Although all strains up-regulated surface MHC class II and B7-2 (CD86), which is indicative of DC maturation, those lactobacilli with greatest capacity to induce IL-12 were most effective. Remarkably, Lactobacillus reuteri DSM12246, a poor IL-12 inducer, inhibited IL-12, IL-6, and TNF-alpha induction by the otherwise strong cytokine inducer L. casei CHCC3139, while IL-10 production remained unaltered. In analogous fashion, L. reuteri reduced L casei-induced up-regulation of B7-2. These results suggest that different species of Lactobacillus exert very different DC activation patterns and, furthermore, at least one species may be capable of inhibiting activities of other species in the genus. Thus, the potential exists for Th1/Th2/Th3-driving capacities of the gut DC to be modulated according to composition of gut microflora, including ingested probiotics.