Plasma-Derived Polyreactive Secretory-Like IgA and IgM Opsonizing Salmonella enterica Typhimurium Reduces Invasion and Gut Tissue Inflammation through Agglutination.
Plasma-Derived Polyreactive Secretory-Like IgA and IgM Opsonizing Salmonella enterica Typhimurium Reduces Invasion and Gut Tissue Inflammation through Agglutination.
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DOI：
10.3389/fimmu.2017.01043
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发表时间：
2017
影响因子：
7.3
通讯作者：
Corthésy B
中科院分区：
文献类型：
--
作者：
Bioley G;Monnerat J;Lötscher M;Vonarburg C;Zuercher A;Corthésy B
由于越来越多的肠道病原菌出现了抗药性菌株，开发替代疗法来对抗肠道感染是一个主要的健康问题。虽然疫苗接种需要抗原、佐剂和递送途径的适当组合才能在粘膜引起保护性免疫，但口服直接主动抗体制剂，即被动免疫，听起来是一个有价值的替代方案。然而，沿着肠道，该策略遇到了难以获得足够数量的抗体的困难，这些抗体具有适当的特异性和分子结构，用于粘膜递送。生理上，在抗体水平上，胃肠粘膜表面对肠道病原体的保护主要是由分泌型IgA和分泌型IgM介导的。我们已经证明，纯化的人血浆来源的IgA和IgM可以与分泌成分结合，产生具有生物活性的分泌样IgA和IgM(SCIgA/M)，在体外可以保护上皮细胞免受福氏志贺菌的感染。在这项研究中，我们旨在评估这些抗体制剂在体内的保护潜力。我们现在证实，这种多反应制剂有效地与肠炎沙门氏菌结合，并触发细菌凝集，如激光扫描共聚焦显微镜所观察到的。当被送入小鼠结扎的肠环后，SCIgA/M介导的聚集体持续存在于肠道环境中，并通过免疫排斥限制细菌进入肠道Peyer‘s补丁。此外，小鼠口服由鼠伤寒沙门氏菌和SCIgA/M组成的免疫复合物可减少粘膜感染、全身扩散和局部炎症。总之，我们的数据为未来评估被动口服多反应性血浆来源的SCIgA/M以对抗各种肠道病原体感染提供了有价值的线索。
Due to the increasing emergence of antibiotic-resistant strains of enteropathogenic bacteria, development of alternative treatments to fight against gut infections is a major health issue. While vaccination requires that a proper combination of antigen, adjuvant, and delivery route is defined to elicit protective immunity at mucosae, oral delivery of directly active antibody preparations, referred to as passive immunization, sounds like a valuable alternative. Along the gut, the strategy suffers, however, from the difficulty to obtain sufficient amounts of antibodies with the appropriate specificity and molecular structure for mucosal delivery. Physiologically, at the antibody level, the protection of gastrointestinal mucosal surfaces against enteropathogens is principally mediated by secretory IgA and secretory IgM. We previously demonstrated that purified human plasma-derived IgA and IgM can be associated with secretory component to generate biologically active secretory-like IgA and IgM (SCIgA/M) that can protect epithelial cells from infection by Shigella flexneri in vitro. In this study, we aimed at evaluating the protective potential of these antibody preparations in vivo. We now establish that such polyreactive preparations bind efficiently to Salmonella enterica Typhimurium and trigger bacterial agglutination, as observed by laser scanning confocal microscopy. Upon delivery into a mouse ligated intestinal loop, SCIgA/M-mediated aggregates persist in the intestinal environment and limit the entry of bacteria into intestinal Peyer’s patches via immune exclusion. Moreover, oral administration to mice of immune complexes composed of S. Typhimurium and SCIgA/M reduces mucosal infection, systemic dissemination, and local inflammation. Altogether, our data provide valuable clues for the future appraisal of passive oral administration of polyreactive plasma-derived SCIgA/M to combat infection by a variety of enteropathogens.