Bifidobacterium infantis 35624 administration induces Foxp3 T regulatory cells in human peripheral blood: potential role for myeloid and plasmacytoid dendritic cells
Bifidobacterium infantis 35624 administration induces Foxp3 T regulatory cells in human peripheral blood: potential role for myeloid and plasmacytoid dendritic cells
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DOI：
10.1136/gutjnl-2011-300936
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发表时间：
2012-03-01
期刊：
影响因子：
24.5
通讯作者：
O'Mahony, Liam
中科院分区：
文献类型：
--
作者：
Konieczna, Patrycja;Groeger, David;O'Mahony, Liam
背景肠道内稳态依赖于对微生物群的免疫耐受目的（1）确定益生菌是否可以诱导人类Foxp 3 T细胞;（2）阐明人树突状细胞诱导Foxp 3 T细胞的分子机制。将单核细胞来源的树突状细胞（MDDC）、髓样树突状细胞（mDC）和浆细胞样树突状细胞（pDC）与B淋巴细胞和自体淋巴细胞体外孵育。结果：B s组外周血中IL-10的分泌选择性增加，Foxp 3的表达增强。在体外，MDDC、mDC和pDC表达吲哚胺2，3-双加氧酶，并分泌IL-10，但不分泌IL-12 p70，以响应B受体。MDDC和mDC IL-10分泌是Toll样受体（TLR）-2/6依赖性的，而pDC IL-10分泌是TLR-9依赖性的。此外，MDDC和mDC表达RALDH 2，其具有TLR-2和DC-SIGN依赖性。B婴儿刺激的MDDC、mDC和pDC诱导T细胞Foxp 3表达。TLR-2，DC-SIGN和视黄酸所需的MDDC和mDC诱导Foxp 3 T细胞，而pDC需要吲哚胺2，3-dioxygenase.Conclusions B的管理，以人类选择性地促进免疫调节反应，这表明，这种微生物可能有治疗效用，在炎症性疾病的患者。多种模式识别受体和代谢途径之间的相互作用决定了先天性和随后的调节性T细胞对B受体的应答。这些发现将营养、微生物群和胃肠道粘膜内耐受性的诱导联系起来。
Background Intestinal homoeostasis is dependent on immunological tolerance to the microbiota.Objective To (1) determine if a probiotic could induce Foxp3 T cells in humans; (2) to elucidate the molecular mechanisms, which are involved in the induction of Foxp3 T cells by human dendritic cells.Design Cytokine secretion and Foxp3 expression were assessed in human volunteers following Bifidobacterium infantis feeding. Monocyte-derived dendritic cells (MDDCs), myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) were incubated in vitro with B infantis and autologous lymphocytes. Transcription factor expression, costimulatory molecule expression, cytokine secretion, retinoic acid and tryptophan metabolism were analysed.Results Volunteers fed B infantis displayed a selective increase in secretion of interleukin (IL)-10 and enhanced Foxp3 expression in peripheral blood. In vitro, MDDCs, mDCs and pDCs expressed indoleamine 2,3-dioxygenase and secreted IL-10, but not IL-12p70, in response to B infantis. MDDC and mDC IL-10 secretion was Toll-like receptor (TLR)-2/6 dependent, while pDC IL-10 secretion was TLR-9 dependent. In addition, MDDCs and mDCs expressed RALDH2, which was TLR-2 and DC-SIGN dependent. B infantis-stimulated MDDCs, mDCs and pDCs induced T cell Foxp3 expression. TLR-2, DC-SIGN and retinoic acid were required for MDDC and mDC induction of Foxp3 T cells, while pDCs required indoleamine 2,3-dioxygenase.Conclusions B infantis administration to humans selectively promotes immunoregulatory responses, suggesting that this microbe may have therapeutic utility in patients with inflammatory disease. Cross-talk between multiple pattern-recognition receptors and metabolic pathways determines the innate and subsequent T regulatory cell response to B infantis. These findings link nutrition, microbiota and the induction of tolerance within the gastrointestinal mucosa.