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Parallelism of intestinal secretory IgA shapes functional microbial fitness
Nature ( IF 64.8 ) Pub Date : 2021-10-13 , DOI: 10.1038/s41586-021-03973-7
Tim Rollenske 1 , Sophie Burkhalter 1 , Lukas Muerner 2 , Stephan von Gunten 2 , Jolanta Lukasiewicz 3 , Hedda Wardemann 4 , Andrew J Macpherson 1
Affiliation  

Dimeric IgA secreted across mucous membranes in response to nonpathogenic taxa of the microbiota accounts for most antibody production in mammals. Diverse binding specificities can be detected within the polyclonal mucosal IgA antibody response1,2,3,4,5,6,7,8,9,10, but limited monoclonal hybridomas have been studied to relate antigen specificity or polyreactive binding to functional effects on microbial physiology in vivo11,12,13,14,15,16,17. Here we use recombinant dimeric monoclonal IgAs (mIgAs) to finely map the intestinal plasma cell response to microbial colonization with a single microorganism in mice. We identify a range of antigen-specific mIgA molecules targeting defined surface and nonsurface membrane antigens. Secretion of individual dimeric mIgAs targeting different antigens in vivo showed distinct alterations in the function and metabolism of intestinal bacteria, largely through specific binding. Even in cases in which the same microbial antigen is targeted, microbial metabolic alterations differed depending on IgA epitope specificity. By contrast, bacterial surface coating generally reduced motility and limited bile acid toxicity. The overall intestinal IgA response to a single microbe therefore contains parallel components with distinct effects on microbial carbon-source uptake, bacteriophage susceptibility, motility and membrane integrity.



中文翻译:

肠道分泌 IgA 的平行性塑造功能性微生物适应性

响应于微生物群的非致病性分类群而跨粘膜分泌的二聚体 IgA 占哺乳动物抗体产生的大部分。在多克隆粘膜 IgA 抗体反应1,2,3,4,5,6,7,8,9,10中可以检测到多种结合特异性,但已经研究了有限的单克隆杂交瘤,将抗原特异性或多反应性结合与功能效应联系起来关于体内微生物生理学11,12,13,14,15,16,17. 在这里,我们使用重组二聚体单克隆 IgAs (mIgAs) 精细绘制小鼠肠道浆细胞对单一微生物定植的反应。我们确定了一系列针对特定表面和非表面膜抗原的抗原特异性 mIgA 分子。体内针对不同抗原的单个二聚体 mIgA 的分泌在肠道细菌的功能和代谢方面表现出明显的变化,主要是通过特异性结合。即使在靶向相同微生物抗原的情况下,微生物代谢改变也因 IgA 表位特异性而异。相比之下,细菌表面涂层通常会降低运动能力并限制胆汁酸毒性。

更新日期:2021-10-13
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