小柯机器人

瑞士伯尔尼大学Andrew J. Macpherson和Tim Rollenske研究组合作发现肠道分泌型 IgA 的平行性塑造功能性微生物适应性。这一研究成果发表在2021年10月13日出版的国际学术期刊《自然》上。

他们使用重组二聚化单克隆 IgAs (mIgAs) 来精细绘制肠道浆细胞对小鼠中单个微生物定植的微生物应答。他们确定了一系列针对确定的表面和非表面膜抗原的抗原特异性 mIgA 分子。体内靶向不同抗原的个体二聚化 mIgAs 的分泌显示出肠道细菌功能和代谢的不同改变，这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，细菌表面衣壳通常会降低运动性并限制胆汁酸毒性。因此，对单一微生物的整体肠道 IgA应答包含对微生物碳源吸收、噬菌体敏感性、运动性和膜完整性具有不同影响的平行成分。

据了解，为影响微生物群的非致病性分类群而跨粘膜分泌的二聚化 IgA 是哺乳动物中大部分抗体产生的原因。在多克隆粘膜 IgA 抗体反应中可以检测到不同的结合特异性，但已经研究了有限的单克隆杂交瘤，将体内微生物生理学的抗原特异性或多反应性结合与功能影响联系起来。

附：英文原文

Title: Parallelism of intestinal secretory IgA shapes functional microbial fitness

Author: Rollenske, Tim, Burkhalter, Sophie, Muerner, Lukas, von Gunten, Stephan, Lukasiewicz, Jolanta, Wardemann, Hedda, Macpherson, Andrew J.

Issue&Volume: 2021-10-13

Abstract: 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.

DOI: 10.1038/s41586-021-03973-7

Source: https://www.nature.com/articles/s41586-021-03973-7

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html