鼠李糖乳杆菌GG及其SpaC菌毛黏附素可调节人类胎儿肠道中的炎症反应和TLR相关基因表达。
Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut.
作者信息
Ganguli Kriston, Collado Maria C, Rautava Jaana, Lu Lei, Satokari Reetta, von Ossowski Ingemar, Reunanen Justus, de Vos Willem M, Palva Airi, Isolauri Erika, Salminen Seppo, Walker W Allan, Rautava Samuli
机构信息
Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, Massachusetts.
1] Functional Foods Forum, University of Turku, Turku, Finland [2] Department of Biotechnology, Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain.
出版信息
Pediatr Res. 2015 Apr;77(4):528-35. doi: 10.1038/pr.2015.5. Epub 2015 Jan 12.
BACKGROUND
Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human fetal intestinal models.
METHODS
Tumor necrosis factor (TNF)-α mRNA expression was measured by qPCR in a human fetal intestinal organ culture model exposed to live L. rhamnosus GG and proinflammatory stimuli. Binding of recombinant SpaC pilus protein to intestinal epithelial cells (IECs) was assessed in human fetal intestinal organ culture and the human fetal intestinal epithelial cell line H4 by immunohistochemistry and immunofluorescence, respectively. TLR-related gene expression in fetal ileal organ culture after exposure to recombinant SpaC was assessed by qPCR.
RESULTS
Live L. rhamnosus GG significantly attenuates pathogen-induced TNF-α mRNA expression in the human fetal gut. Recombinant SpaC protein was found to adhere to the fetal gut and to modulate varying levels of TLR-related gene expression.
CONCLUSION
The human fetal gut is responsive to luminal microbes. L. rhamnosus GG significantly attenuates fetal intestinal inflammatory responses to pathogenic bacteria. The L. rhamnosus GG pilus adhesin SpaC binds to immature human IECs and directly modulates IEC innate immune gene expression.
背景
子宫内的细菌接触可调节胎儿和新生儿的免疫反应。母体补充益生菌可降低婴儿患免疫介导疾病的风险。我们在人类胎儿肠道模型中研究了活的鼠李糖乳杆菌GG及其SpaC菌毛粘附素的免疫调节特性。
方法
在暴露于活的鼠李糖乳杆菌GG和促炎刺激的人类胎儿肠道器官培养模型中，通过qPCR测量肿瘤坏死因子（TNF）-α mRNA表达。分别通过免疫组织化学和免疫荧光在人类胎儿肠道器官培养物和人类胎儿肠道上皮细胞系H4中评估重组SpaC菌毛蛋白与肠道上皮细胞（IEC）的结合。通过qPCR评估暴露于重组SpaC后胎儿回肠器官培养物中TLR相关基因的表达。
结果
活的鼠李糖乳杆菌GG可显著减弱病原体诱导的人类胎儿肠道中TNF-α mRNA的表达。发现重组SpaC蛋白可粘附于胎儿肠道并调节不同水平的TLR相关基因表达。
结论
人类胎儿肠道对腔内微生物有反应。鼠李糖乳杆菌GG可显著减弱胎儿肠道对病原菌的炎症反应。鼠李糖乳杆菌GG菌毛粘附素SpaC与未成熟的人类IEC结合并直接调节IEC先天免疫基因表达。
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