New Nature Paper by the Wetter Slack Group

High-avidity IgA protects the intestine by enchaining growing bacteria.

by Markus Christian Schlumberger

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, Blanda 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.

Nature. 2017 Apr 12, doi: 10.1038/nature22058.

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'). 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 densities (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.

external page>> Publication

ETH News Article: Chaining up diarrhoae pathogens

JavaScript has been disabled in your browser