Secretory IgA is Concentrated in the Outer Layer of Colonic Mucus along with Gut Bacteria
Secretory IgA is Concentrated in the Outer Layer of Colonic Mucus along with Gut Bacteria
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DOI：
10.3390/pathogens3020390
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发表时间：
2014-06-01
期刊：
影响因子：
3.7
通讯作者：
Kaetzel, Charlotte S.
中科院分区：
文献类型：
--
作者：
Rogier, Eric W.;Frantz, Aubrey L.;Kaetzel, Charlotte S.
分泌伊加（SIgA）类的抗体构成抗原特异性免疫防御的第一线，防止细菌和病原微生物及其分泌产物进入身体。除了预防感染外，SIgA还可以塑造肠道微生物组的组成。SIgA通过多聚免疫球蛋白受体（pIgR）跨肠上皮细胞转运到肠道分泌物中。上皮表面由厚的粘液网络保护，该粘液网络由致密的无菌内层和由肠道细菌定殖的松散外层组成。小鼠和人类结肠组织的免疫荧光显微镜显示，SIgA与肠道细菌共定位于外粘液层。使用pIgR和/或粘蛋白-2（Muc 2，肠粘液的主要糖蛋白）遗传缺陷的小鼠，我们发现Muc 2而不是SIgA是从结肠内粘液层排除肠道细菌所必需的。我们的研究结果支持一种模型，即SIgA通过与粘蛋白和肠道细菌的联合相互作用锚定在结肠粘液的外层，从而提供针对病原体的免疫保护，同时保持与肠道菌的互利关系。
Antibodies of the secretory IgA (SIgA) class comprise the first line of antigen-specific immune defense, preventing access of commensal and pathogenic microorganisms and their secreted products into the body proper. In addition to preventing infection, SIgA shapes the composition of the gut microbiome. SIgA is transported across intestinal epithelial cells into gut secretions by the polymeric immunoglobulin receptor (pIgR). The epithelial surface is protected by a thick network of mucus, which is composed of a dense, sterile inner layer and a loose outer layer that is colonized by commensal bacteria. Immunofluorescence microscopy of mouse and human colon tissues demonstrated that the SIgA co-localizes with gut bacteria in the outer mucus layer. Using mice genetically deficient for pIgR and/or mucin-2 (Muc2, the major glycoprotein of intestinal mucus), we found that Muc2 but not SIgA was necessary for excluding gut bacteria from the inner mucus layer in the colon. Our findings support a model whereby SIgA is anchored in the outer layer of colonic mucus through combined interactions with mucin proteins and gut bacteria, thus providing immune protection against pathogens while maintaining a mutually beneficial relationship with commensals.