R&D Laboratory of the Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon, 1011 Lausanne, Switzerland.
J Biol Chem. 2010 Oct 29;285(44):33906-13. doi: 10.1074/jbc.M110.135111. Epub 2010 Aug 20.
The precise mechanisms underlying the interaction between intestinal bacteria and the host epithelium lead to multiple consequences that remain poorly understood at the molecular level. Deciphering such events can provide valuable information as to the mode of action of commensal and probiotic microorganisms in the gastrointestinal environment. Potential roles of such microorganisms along the privileged target represented by the mucosal immune system include maturation prior, during and after weaning, and the reduction of inflammatory reactions in pathogenic conditions. Using human intestinal epithelial Caco-2 cell grown as polarized monolayers, we found that association of a Lactobacillus or a Bifidobacterium with nonspecific secretory IgA (SIgA) enhanced probiotic adhesion by a factor of 3.4-fold or more. Bacteria alone or in complex with SIgA reinforced transepithelial electrical resistance, a phenomenon coupled with increased phosphorylation of tight junction proteins zonula occludens-1 and occludin. In contrast, association with SIgA resulted in both enhanced level of nuclear translocation of NF-κB and production of epithelial polymeric Ig receptor as compared with bacteria alone. Moreover, thymic stromal lymphopoietin production was increased upon exposure to bacteria and further enhanced with SIgA-based complexes, whereas the level of pro-inflammatory epithelial cell mediators remained unaffected. Interestingly, SIgA-mediated potentiation of the Caco-2 cell responsiveness to the two probiotics tested involved Fab-independent interaction with the bacteria. These findings add to the multiple functions of SIgA and underscore a novel role of the antibody in interaction with intestinal bacteria.
肠道细菌与宿主上皮细胞相互作用的确切机制导致了多种后果,这些后果在分子水平上仍知之甚少。破译这些事件可以提供有价值的信息,了解共生菌和益生菌微生物在胃肠道环境中的作用模式。这些微生物在黏膜免疫系统这一重要靶点上的潜在作用包括在断奶前、期间和之后的成熟,以及减少在致病条件下的炎症反应。我们用人肠上皮细胞 Caco-2 进行培养,使其成为极化单层细胞,发现乳酸杆菌或双歧杆菌与非特异性分泌型免疫球蛋白 A(SIgA)的结合使益生菌的黏附增强了 3.4 倍或更多。细菌本身或与 SIgA 结合增强了跨上皮电阻,这一现象与紧密连接蛋白闭合蛋白-1 和闭合蛋白的磷酸化增加有关。相比之下,与 SIgA 结合导致核内 NF-κB 的易位水平和上皮多聚免疫球蛋白受体的产生都比单独的细菌增强。此外,暴露于细菌后胸腺基质淋巴细胞生成素的产生增加,并且与基于 SIgA 的复合物进一步增强,而上皮细胞促炎介质的水平保持不变。有趣的是,SIgA 介导的对两种益生菌的 Caco-2 细胞反应性的增强涉及与细菌的 Fab 非依赖性相互作用。这些发现增加了 SIgA 的多种功能,并强调了抗体在与肠道细菌相互作用中的新作用。