Flagellar-based motility accelerates IgA-mediated agglutination of Salmonella Typhimurium at high bacterial cell densities.
Flagellar-based motility accelerates IgA-mediated agglutination of Salmonella Typhimurium at high bacterial cell densities.
复制标题
鞭毛为基础的运动加速iga介导的鼠伤寒沙门菌在高细菌细胞密度下的凝集。
DOI：
10.3389/fimmu.2023.1193855
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
分泌型 IgA (SIgA) 通过免疫排斥过程保护肠道上皮免受肠病原体的侵害，例如鼠伤寒沙门氏菌 (STm)，其中入侵的细菌通过抗体交联聚集，包裹在粘液中，然后通过蠕动从肠道清除。在高细胞密度下，STm 聚集体形成紧密堆积的网络，让人想起早期的细菌生物膜。然而，目前尚不清楚 SIgA 如何介导 STm 从运动和侵袭状态到无毒固着状态的转变。在本报告中，我们开发并验证了一种称为“雪球”测定的方法，能够通过小鼠单克隆 IgA Sal4 对 STm 凝集进行实时成像和定量。我们观察到雪球测定中的凝集是剂量依赖性的、抗原特异性的，并且受到抗体同种型的影响。我们确定，基于鞭毛的运动是凝集快速发生的先决条件，即使在细胞与细胞接触频繁的高细胞密度下也是如此。我们还研究了先前与 Sal4 IgA 介导的凝集运动和生物膜形成有关的单个环二 GMP 代谢酶的作用。综上所述，我们的结果表明 IgA 介导的凝集是一个受细菌运动和细胞间碰撞影响的动态过程。我们的结论是，雪球测定是进一步破译驱动这种相互作用的分子和遗传决定因素的可行平台。
Secretory IgA (SIgA) protects the intestinal epithelium from enteric pathogens such as Salmonella enterica serovar Typhimurium (STm) through a process known as immune exclusion, where invading bacteria are aggregated via antibody cross-linking, encased in mucus, and then cleared from the intestinal tract via peristalsis. At high cell densities, the STm aggregates form a tightly packed network that is reminiscent of early bacterial biofilms. However, the underlying mechanism of how SIgA mediates this transition from a motile and invasive state to an avirulent sessile state in STm is currently unknown. In this report, we developed and validated a methodology known as the “snow globe” assay to enable real-time imaging and quantification of STm agglutination by the mouse monoclonal IgA Sal4. We observed that agglutination in the snow globe assay was dose-dependent, antigen-specific, and influenced by antibody isotype. We determined that flagellar-based motility was a prerequisite for rapid onset of agglutination, even at high cell densities where cell-cell contacts are expected to be frequent. We also investigated the roles of individual cyclic-di-GMP metabolizing enzymes previously implicated in motility and biofilm formation in Sal4 IgA-mediated agglutination. Taken together, our results demonstrate that IgA-mediated agglutination is a dynamic process influenced by bacterial motility and cell-cell collisions. We conclude that the snow globe assay is a viable platform to further decipher the molecular and genetic determinants that drive this interaction.
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影响因子：
28.3
作者：
Diard M;Bakkeren E;Lentsch V;Rocker A;Bekele NA;Hoces D;Aslani S;Arnoldini M;Böhi F;Schumann-Moor K;Adamcik J;Piccoli L;Lanzavecchia A;Stadtmueller BM;Donohue N;van der Woude MW;Hockenberry A;Viollier PH;Falquet L;Wüthrich D;Bonfiglio F;Loverdo C;Egli A;Zandomeneghi G;Mezzenga R;Holst O;Meier BH;Hardt WD;Slack E
通讯作者：
Slack E
影响因子：
6.7
作者：
El-Kirat-Chatel S;Beaussart A;Vincent SP;Abellán Flos M;Hols P;Lipke PN;Dufrêne YF
通讯作者：
Dufrêne YF
影响因子：
3.4
作者：
Porter, Michael K.;Steinberg, Asher Preska;Ismagilov, Rustem F.
通讯作者：
Ismagilov, Rustem F.
影响因子：
29.4
作者：
MICHETTI, P;PORTA, N;NEUTRA, MR
通讯作者：
NEUTRA, MR
影响因子：
48
作者：
Choi, KH;Gaynor, JB;Schweizer, HP
通讯作者：
Schweizer, HP