Disparate Effects of Bacteria and Toll-Like Receptor-Dependant Bacterial Ligand Stimulation on Immunoglobulin A Transcytosis

Disparate Effects of Bacteria and Toll-Like Receptor-Dependant Bacterial Ligand Stimulation on Immunoglobulin A Transcytosis
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DOI:
10.1097/ta.0b013e31820c780e
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发表时间:
2011-03-01
影响因子:
--
通讯作者:
Liberati, David M.
Liberati, David M.
中科院分区:
其他
文献类型:
--
作者:
Diebel, Lawrence N.;Liberati, David M.

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背景资料:最近的研究表明,肠道和其他粘膜表面的上皮细胞在协调宿主对管腔微生物的反应中起重要作用。肠上皮细胞在通过多聚免疫球蛋白受体(pIgR)转运二聚分泌型免疫球蛋白A(伊加)中也起重要作用。最终产物是分泌型伊加,其含有称为分泌组分的pIgR的裂解部分。dIgA的转胞吞作用可响应于各种刺激。我们研究了革兰氏阴性(G-)或革兰氏阳性(G+)和Toll样受体(TLR)细菌配体途径对伊加转胞吞作用的影响。将大鼠dIgA加入HT-29细胞单层和细胞的基底室中,然后用热灭活的大肠杆菌(Delta E. coli)、LPS(TLR-4途径配体)、热灭活金黄色葡萄球菌(Delta S.金黄色葡萄球菌)或肽聚糖(TLR-2途径配体)。通过ELISA测定伊加转胞吞作用。流式细胞术和Western blot检测pIgR的表达。结果:用Delta E刺激HT-29细胞的跨上皮电阻,可以促进HT-29细胞的胞吞。coli或LPS。这部分是由于上调pIgR的表达和dIgA-pIgR complexes.Conclusion增强细胞内贩运不同的细菌和TLR-4与TLR-2途径之间的不同影响可能有影响宿主反应在粘膜表面。
Background: Recent studies have indicated that epithelial cells of the gut and other mucosal surfaces play an important role in orchestrating host responses to luminal microbes. Intestinal epithelial cells also play an important role in the transport of dimeric secretory immunoglobulin A (IgA) through the polyimmunoglobulin receptor (pIgR). The end product is secretory IgA, which contains a cleaved portion of the pIgR called secretory component. Transcytosis of dIgA may be responsive to various stimuli. We studied the effect of gram-negative (G-) or gram-positive (G+) and Toll-like receptor (TLR) bacterial ligand pathways on IgA transcytosis in vitro.Methods: Polarized HT-29 cells, a human intestinal epithelial cell line, were grown to confluence ion a two-chamber cell culture system. Rat dIgA was added to the basal chamber of HT-29 cell monolayers and cells and then stimulated with heat-killed Escherichia coli (Delta E. coli), LPS (TLR-4 pathway ligand), heat-killed Staphylococcus aureus (Delta S. aureus), or peptidoglycan (TLR-2 pathway ligand). IgA transcytosis was determined by ELISA. The pIgR expression was quantitated by flow cytometry and Western blot. HT-29 cell monolayer integrity was monitored by serial measurement of transepithelial electrical resistance.Results: Transcytosis was stimulated by either Delta E. coli or LPS. This was in part due to upregulation of pIgR expression and augmented intracellular trafficking of dIgA-pIgR complexes.Conclusion: The disparate effects between different bacteria and TLR-4 versus TLR-2 pathways may have implications in host responses at mucosal surfaces.