Oral Passive Immunization With Plasma-Derived Polyreactive Secretory-Like IgA/M Partially Protects Mice Against Experimental Salmonellosis
Oral Passive Immunization With Plasma-Derived Polyreactive Secretory-Like IgA/M Partially Protects Mice Against Experimental Salmonellosis
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DOI：
10.3389/fimmu.2018.02970
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发表时间：
2018-12-18
影响因子：
7.3
通讯作者：
Bioley, Gilles
中科院分区：
文献类型：
--
作者：
Corthesy, Blaise;Monnerat, Justine;Bioley, Gilles
分泌型免疫球蛋白在胃肠道防御中具有关键作用，并且已知其通过防止细菌获得而起作用。使用肠道沙门氏菌伤寒沙门氏菌细菌感染的严格小鼠模型来检查由口服被动免疫介导的保护作用，所述口服被动免疫是用人血浆来源的多反应性伊加和IgM抗体（Abs）重构为分泌样免疫球蛋白（SCIgA/M）。该试剂已被证明可触发沙门氏菌凝集，并通过免疫排斥限制细菌进入肠道派尔集合淋巴结。我们现在证明，在给药到结扎的肠袢中时，SCIgA/M正确地锚定在粘液中，并且在比伊加/M或IgG更好的程度上被保护免于降解。此外，在用S.肠伤寒沙门氏菌允许保护受感染的动物，如通过粘膜和全身隔室的定殖减少以及肠组织的保存完整性所反映的。与伊加/M或IgG给药相比，SCIgA/M提供了最高程度的保护。此外，在SCIgA/M的治疗性口服递送后也观察到这种保护功效。被动递送SCIgA/M的预防性或治疗性治疗确保了高达50%的感染小鼠的存活率，而未治疗的动物全部死亡。我们的研究结果揭示了口服被动免疫与血浆衍生的多反应性SCIgA/M抗体对抗胃肠道感染的潜力。
Secretory immunoglobulins have a critical role in defense of the gastrointestinal tract and are known to act by preventing bacterial acquisition. A stringent murine model of bacterial infection with Salmonella enterica Typhimurium was used to examine protection mediated by oral passive immunization with human plasma-derived polyreactive IgA and IgM antibodies (Abs) reconstituted as secretory-like immunoglobulins (SCIgA/M). This reagent has been shown to trigger Salmonella agglutination and to limit the entry of bacterium into intestinal Peyer's patches via immune exclusion. We now demonstrate that upon administration into ligated intestinal loops, SCIgA/M properly anchors in the mucus and is protected from degradation to a better extent that IgA/M or IgG. Moreover, prophylactic oral administration of SCIgA/M before intragastric infection of mice with a virulent strain of S. enterica Typhimurium allows to protect infected animals, as reflected by reduced colonization of both mucosal and systemic compartments, and conserved integrity of intestinal tissues. In comparison with IgA/M or IgG administration, SCIgA/M provided the highest degree of protection. Moreover, such protective efficacy is also observed after therapeutic oral delivery of SCIgA/M. Either prophylactic or therapeutic treatment with passively delivered SCIgA/M ensured survival of up to 50% of infected mice, while untreated animals all died. Our findings unravel the potential of oral passive immunization with plasma-derived polyreactive SCIgA/M Abs to fight gastrointestinal infections.