Department of Systems Biology, Technical University of Denmark, Center for Biological Sequence Analysis, 2800 Kgs, Lyngby, Denmark.
BMC Immunol. 2010 Jan 19;11:2. doi: 10.1186/1471-2172-11-2.
The first exposure to microorganisms at mucosal surfaces is critical for immune maturation and gut health. Facultative anaerobic bacteria are the first to colonise the infant gut, and the impact of these bacteria on intestinal epithelial cells (IEC) may be determinant for how the immune system subsequently tolerates gut bacteria.
To mirror the influence of the very first bacterial stimuli on infant IEC, we isolated IEC from mouse foetuses at gestational day 19 and from germfree neonates. IEC were stimulated with gut-derived bacteria, Gram-negative Escherichia coli Nissle and Gram-positive Lactobacillus acidophilus NCFM, and expression of genes important for immune regulation was measured together with cytokine production. E. coli Nissle and L. acidophilus NCFM strongly induced chemokines and cytokines, but with different kinetics, and only E. coli Nissle induced down-regulation of Toll-like receptor 4 and up-regulation of Toll-like receptor 2. The sensitivity to stimulation was similar before and after birth in germ-free IEC, although Toll-like receptor 2 expression was higher before birth than immediately after.
In conclusion, IEC isolated before gut colonisation occurs at birth, are highly responsive to stimulation with gut commensals, with L. acidophilus NCFM inducing a slower, but more sustained response than E. coli Nissle. E. coli may induce intestinal tolerance through very rapid up-regulation of chemokine and cytokine genes and down-regulation of Toll-like receptor 4, while regulating also responsiveness to Gram-positive bacteria.
黏膜表面首次接触微生物对免疫成熟和肠道健康至关重要。兼性厌氧菌是最早定植于婴儿肠道的细菌，这些细菌对肠上皮细胞（IEC）的影响可能决定了免疫系统随后对肠道细菌的耐受程度。
为了模拟最初细菌刺激对婴儿 IEC 的影响，我们从妊娠第 19 天的胎鼠和无菌新生鼠中分离出 IEC。用肠道来源的细菌，革兰氏阴性大肠杆菌 Nissle 和革兰氏阳性嗜酸乳杆菌 NCFM 刺激 IEC，并测量与免疫调节相关的基因表达和细胞因子产生。E. coli Nissle 和 L. acidophilus NCFM 强烈诱导趋化因子和细胞因子，但具有不同的动力学，只有 E. coli Nissle 诱导 Toll 样受体 4 下调和 Toll 样受体 2 上调。无菌 IEC 出生前后的刺激敏感性相似，尽管出生前 Toll 样受体 2 的表达高于出生后立即。
总之，在出生前肠道定植之前分离的 IEC 对肠道共生菌的刺激反应非常敏感，L. acidophilus NCFM 诱导的反应比 E. coli Nissle 缓慢，但更持久。E. coli 可能通过快速上调趋化因子和细胞因子基因以及下调 Toll 样受体 4 来诱导肠道耐受，同时还调节对革兰氏阳性细菌的反应性。
