Recombinant Human Secretory IgA Induces Salmonella Typhimurium Agglutination and Limits Bacterial Invasion into Gut-Associated Lymphoid Tissues.
Recombinant Human Secretory IgA Induces Salmonella Typhimurium Agglutination and Limits Bacterial Invasion into Gut-Associated Lymphoid Tissues.
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DOI：
10.1021/acsinfecdis.0c00842
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发表时间：
2021-05-14
影响因子：
5.3
通讯作者：
Mantis NJ
中科院分区：
文献类型：
--
作者：
Richards AF;Baranova DE;Pizzuto MS;Jaconi S;Willsey GG;Torres-Velez FJ;Doering JE;Benigni F;Corti D;Mantis NJ
作为粘膜分泌物、人初乳和母乳中的主要抗体类型，分泌型 IgA (SIgA) 在保护新生儿肠上皮免受革兰氏阴性菌鼠伤寒沙门氏菌 (STm) 等侵袭性肠道病原体侵害方面发挥着核心作用。 SIgA 是一种复杂的分子，由两个或多个 IgA 单体、连接 (J) 链和分泌成分 (SC) 的组合组成，其中和病原体的确切功能才刚刚开始被阐明。在这项研究中，我们生产并鉴定了 Sal4 的重组人 SIgA 变体，这是一种经过充分鉴定的单克隆抗体 (mAb)，对 STm 脂多糖 (LPS) 的 O5 抗原具有特异性。我们通过流式细胞术、光学显微镜和荧光显微镜证明 Sal4 SIgA 在体外促进大而密集的细菌聚集体的形成。在小鼠模型中，被动口服 Sal4 SIgA 足以将 STm 捕获在肠腔内，并将细菌侵入肠道相关淋巴组织的数量减少几个数量级。 Sal4 SIgA 处理在肠腔中诱导的细菌聚集体难以进行免疫组织化学染色，表明细菌被包裹在保护性胶囊中。事实上，结晶紫染色测定表明，即使短时间暴露于 Sal4 SIgA，STm 也会分泌富含纤维素的细胞外基质。总的来说，这些结果表明重组人 SIgA 概括了与粘膜免疫相关的关键生物活性，并提出了口服被动免疫对抗肠道疾病的前景。
As the predominant antibody type in mucosal secretions, human colostrum, and breast milk, secretory IgA (SIgA) plays a central role in safeguarding the intestinal epithelium of newborns from invasive enteric pathogens like the Gram-negative bacterium Salmonella enterica serovar Typhimurium (STm). SIgA is a complex molecule, consisting of an assemblage of two or more IgA monomers, joining (J)-chain, and secretory component (SC), whose exact functions in neutralizing pathogens are only beginning to be elucidated. In this study, we produced and characterized a recombinant human SIgA variant of Sal4, a well-characterized monoclonal antibody (mAb) specific for the O5-antigen of STm lipopolysaccharide (LPS). We demonstrate by flow cytometry, light microscopy, and fluorescence microscopy that Sal4 SIgA promotes the formation of large, densely packed bacterial aggregates in vitro. In a mouse model, passive oral administration of Sal4 SIgA was sufficient to entrap STm within the intestinal lumen and reduce bacterial invasion into gut-associated lymphoid tissues by several orders of magnitude. Bacterial aggregates induced by Sal4 SIgA treatment in the intestinal lumen were recalcitrant to immunohistochemical staining, suggesting the bacteria were encased in a protective capsule. Indeed, a crystal violet staining assay demonstrated that STm secretes an extracellular matrix enriched in cellulose following even short exposures to Sal4 SIgA. Collectively, these results demonstrate that recombinant human SIgA recapitulates key biological activities associated with mucosal immunity and raises the prospect of oral passive immunization to combat enteric diseases.
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影响因子：
6.4
作者：
Freedman, DJ;Tacket, CO;Crabb, JH
通讯作者：
Crabb, JH
影响因子：
7.7
作者：
Kumar Bharathkar S;Parker BW;Malyutin AG;Haloi N;Huey-Tubman KE;Tajkhorshid E;Stadtmueller BM
通讯作者：
Stadtmueller BM
DOI：
10.1084/jem.139.5.1189
发表时间：
1974-05-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Carter PB;Collins FM
通讯作者：
Collins FM
影响因子：
7.3
作者：
Bioley G;Monnerat J;Lötscher M;Vonarburg C;Zuercher A;Corthésy B
通讯作者：
Corthésy B
影响因子：
7.3
作者：
Corthesy, Blaise;Monnerat, Justine;Bioley, Gilles
通讯作者：
Bioley, Gilles