Secretory IgA-Mediated Neutralization of Shigella flexneri Prevents Intestinal Tissue Destruction by Down-Regulating Inflammatory Circuits
Secretory IgA-Mediated Neutralization of Shigella flexneri Prevents Intestinal Tissue Destruction by Down-Regulating Inflammatory Circuits
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DOI：
10.4049/jimmunol.0901838
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发表时间：
2009-11-01
影响因子：
4.4
通讯作者：
Phalipon, Armelle
中科院分区：
文献类型：
--
作者：
Boullier, Severine;Tanguy, Myriam;Phalipon, Armelle
志贺氏菌是一种革兰氏阴性的侵袭性肠道致病菌，可引起细菌性痢疾，导致人类结肠粘膜的破裂、侵袭和炎性破坏。我们探讨了由志贺氏菌LPS特异性分泌型伊加（SIgA）介导的保护机制，SIgA是自然感染后诱导的主要粘膜抗体。细菌、SIgA或SIgA-S。将弗氏免疫复合物施用于含有派尔集合淋巴结的兔结扎肠环中。8 h后，细菌、SIgA和SIgA-S的定位。通过免疫组织化学和共聚焦显微镜成像检查福氏免疫复合物。我们发现，抗志贺氏菌LPS SIgA，主要通过免疫排斥，防止志贺氏菌引起的炎症负责破坏肠道屏障。除了这种管腔捕获，一小部分SIgA-S。显示福氏免疫复合物进入兔派尔集合淋巴结并被上皮下圆顶区域的树突状细胞内化。使用新设计的兔促炎和抗炎介质基因引物，通过定量RT-PCR分析局部炎症状态。在暴露于免疫复合物的派伊尔集合淋巴结中，观察到促炎基因（包括TNF-α、IL-6、考克斯-2和IFN-γ）表达的有限上调，与保留的形态一致。相比之下，在Peyer氏斑暴露于单独的志贺氏菌，相同的介质的高表达被测量，表明中和SIgA抑制志贺氏菌的促炎特性。这些结果表明，以免疫复合物的形式，SIgA保证了免疫排斥和易位细菌的中和，从而通过防止细菌诱导的炎症来保持肠道屏障的完整性。这些发现增加了SIgA非炎症特性的多个方面。免疫学杂志，2009，183：5879-5885.
Shigella, a Gram-negative invasive enteropathogenic bacterium responsible for bacillary dysentery, causes the rupture, invasion, and inflammatory destruction of the human colonic mucosa. We explored the mechanisms of protection mediated by Shigella LPS-specific secretory IgA (SIgA), the major mucosal Ab induced upon natural infection. Bacteria, SIgA, or SIgA-S. flexneri immune complexes were administered into rabbit ligated intestinal loops containing a Peyer's patch. After 8 h, localizations of bacteria, SIgA, and SIgA-S. flexneri immune complexes were examined by immunohistochemistry and confocal microscopy imaging. We found that anti-Shigella LPS SIgA, mainly via immune exclusion, prevented Shigella-induced inflammation responsible for the destruction of the intestinal barrier. Besides this luminal trapping, a small proportion of SIgA-S. flexneri immune complexes were shown to enter the rabbit Peyer's patch and were internalized by dendritic cells of the subepithelial dome region. Local inflammatory status was analyzed by quantitative RT-PCR using newly designed primers for rabbit pro- and anti-inflammatory mediator genes. In Peyer's patches exposed to immune complexes, limited up-regulation of the expression of proinflammatory genes, including TNF-alpha, IL-6, Cox-2, and IFN-gamma, was observed, consistent with preserved morphology. In contrast, in Peyer's patches exposed to Shigella alone, high expression of the same mediators was measured, indicating that neutralizing SIgA dampens the proinflammatory properties of Shigella. These results show that in the form of immune complexes, SIgA guarantees both immune exclusion and neutralization of translocated bacteria, thus preserving the intestinal barrier integrity by preventing bacterial-induced inflammation. These findings add to the multiple facets of the noninflammatory properties of SIgA. The Journal of Immunology, 2009, 183: 5879-5885.