Role of postnatal acquisition of the intestinal microbiome in the early development of immune function.
Role of postnatal acquisition of the intestinal microbiome in the early development of immune function.
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DOI：
10.1097/mpg.0b013e3181e1a114
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发表时间：
2010-09
影响因子：
2.9
通讯作者：
Lorenz RG
中科院分区：
文献类型：
--
作者：
Dimmitt RA;Staley EM;Chuang G;Tanner SM;Soltau TD;Lorenz RG
使用广谱抗生素治疗是早产儿的常见做法。这种治疗可以减少粪便微生物群的生物多样性，可能是坏死性小肠结肠炎（NEC）的原因之一。相反，益生菌治疗早产儿可降低NEC的发生率。我们假设这些观察结果的一个机制是细菌对出生后粘膜免疫系统发育的影响。采用实时荧光定量PCR技术研究了免疫分子和微生物传感器在出生后小鼠胃肠道中的表达。随后，比较两周龄无特定病原体（SPF）和微生物减少（抗生素处理，MR）小鼠的免疫分子和微生物传感器表达、肠系膜淋巴结（MLN）T细胞数量和活化、肠屏障功能/渗透性、全身淋巴细胞数量和T细胞表型定型。Toll样受体（TLR）2，4和5在2周龄SPF小鼠中表达最高，而在MR小鼠中表达降低。通过FITC-葡聚糖摄取评估，肠紧密连接功能没有差异，但MR小鼠增加了穿过肠上皮屏障的细菌移位。MR小鼠的脾脏B细胞和MLN CD 4 + T细胞显著减少，但脾脏T细胞数量正常。来自MR小鼠的这些全身性T细胞产生更多的IL-4，以及更少的干扰素-γ和IL-17，表明胎儿T辅助细胞2型表型的维持。这项研究表明，肠道微生物群对出生后早期免疫发育有影响。确定对这种发展至关重要的特定细菌和/或细菌配体可以深入了解广谱抗生素和/或益生菌治疗影响粘膜免疫系统和粘膜相关疾病发展的机制。
Therapy with broad-spectrum antibiotics is a common practice for premature infants. This treatment can reduce the biodiversity of the fecal microbiota and may be a factor in the cause of necrotizing enterocolitis (NEC). In contrast, probiotic treatment of premature infants reduces the incidence of NEC. We hypothesized that one mechanism for these observations is the influence of bacteria on postnatal development of the mucosal immune system. Expression of immune molecules and microbial sensors was investigated in the postnatal mouse gastrointestinal tract by real-time PCR. Subsequently, two-week-old specific pathogen free (SPF) and microbial reduced (antibiotic treated, MR) mice were compared for immune molecule and microbial sensor expression, mesenteric lymph node (MLN) T-cell numbers and activation, intestinal barrier function/permeability, systemic lymphocyte numbers, and T-cell phenotype commitment. Toll-like receptor (TLR) 2, 4, and 5 expression was highest in 2-week-old SPF mice, and this expression was decreased in MR mice. There was no difference in intestinal tight-junctional function, as evaluated by FITC-dextran uptake, but MR mice had increased bacteria translocation across the intestinal epithelial barrier. MR mice had significantly fewer splenic B-cells and MLN CD4+ T-cells, but there were normal numbers of splenic T-cells. These systemic T-cells from MR mice produced more IL-4, and less interferon-γ and IL-17, indicative of a maintenance of the fetal, T-helper cell type 2 phenotype. This study shows that intestinal commensal microbiota have an influence on early postnatal immune development. Determining specific bacteria and/or bacterial ligands critical for this development could provide insight into the mechanisms by which broad-spectrum antibiotics and/or probiotic therapy influences the development of the mucosal immune system and mucosal-related diseases.