高亲和力IgA通过“束缚”生长中的细菌从而保护肠道
Title：
High-avidity IgA protects the intestine by enchaining growing bacteria
Abstract：
Vaccine-induced high-avidity IgA can protect against bacterial enteropathogens by directly neutralizing virulence factors or by poorly defined mechanisms that physically impede bacterial interactions with the gut tissues (‘immune exclusion’)1, 2, 3. IgA-mediated cross-linking clumps bacteria in the gut lumen and is critical for protection against infection by non-typhoidal Salmonella enterica subspecies enterica serovar Typhimurium (S. Typhimurium). However, classical agglutination, which was thought to drive this process, is efficient only at high pathogen densities (≥108 non-motile bacteria per gram). In typical infections, much lower densities4, 5 (100–107 colony-forming units per gram) of rapidly dividing bacteria are present in the gut lumen. Here we show that a different physical process drives formation of clumps in vivo: IgA-mediated cross-linking enchains daughter cells, preventing their separation after division, and clumping is therefore dependent on growth. Enchained growth is effective at all realistic pathogen densities, and accelerates pathogen clearance from the gut lumen. Furthermore, IgA enchains plasmid-donor and -recipient clones into separate clumps, impeding conjugative plasmid transfer in vivo. Enchained growth is therefore a mechanism by which IgA can disarm and clear potentially invasive species from the intestinal lumen without requiring high pathogen densities, inflammation or bacterial killing. Furthermore, our results reveal an untapped potential for oral vaccines in combating the spread of antimicrobial resistance.
All Authors：
Kathrin Moor, Médéric Diard, Mikael E Sellin, Boas Felmy, Sandra Y Wotzka, Albulena Toska, Erik Bakkeren, Markus Arnoldini, Florence Bansept, Alma Dal Co, Tom Völler, Andrea Minola, Blanca Fernandez-Rodriguez, Gloria Agatic, Sonia Barbieri, Luca Piccoli, Costanza Casiraghi, Davide Corti, Antonio Lanzavecchia, Roland R Regoes, Claude Loverdo, Roman Stocker, Douglas R Brumley, Wolf-Dietrich Hardt , Emma Slack
First Authors：
Douglas R Brumley, Wolf-Dietrich Hardt , Emma Slack
Correspondence：
Kathrin Moor
内容要点：
1、传统的凝集反应仅在病原菌密度较高时发生，细菌间的碰撞伴随着高亲和力IgA介导的交联反应使细菌成簇聚集；
2、病原菌密度较低时，IgA介导的交联反应束缚了细菌分裂时产生的子细胞，抑制了子细胞的分离，随后细菌继续生长导致了细菌成簇聚集；
3、IgA介导的束缚细菌子细胞分离的过程在所有真实的病原菌密度环境下均有效；且促进了肠道内腔的病原菌清除；
4、IgA将质粒供体细菌与受体细菌隔离在不同的细菌簇内，抑制了体内质粒的接合转移。