High-avidity IgA protects the intestine by enchaining growing bacteria

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Moor, K., Diard, M., Sellin, M.-E., Felmy, B., Wotzka, S.-Y., Toska, A., Bakkeren, E., Arnoldini, M., Bansept, F., Dal Co, A., Voller, T., Minola, A., Fernandez-Rodriguez, B., Agatic, G., Barbieri, S., Piccoli, L., Casiraghi, C., Corti, D., Lanzavecchia, A., Regoes, R.-R., Loverdo, C., Stocker, R., Brumley, D.-R., Hardt, W.-D., & Slack, E. (2017). High-avidity IgA protects the intestine by enchaining growing bacteria. Nature, 544(7651). https://doi.org/10.1038/nature22058

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@article{Moor2017_295,
  author = {Moor, Kathrin and Diard, Mederic and Sellin, Mikael E. and Felmy, Boas and Wotzka, Sandra Y. and Toska, Albulena and Bakkeren, Erik and Arnoldini, Markus and Bansept, Florence and Dal Co, Alma and Voller, Tom and Minola, Andrea and Fernandez-Rodriguez, Blanca and Agatic, Gloria and Barbieri, Sonia and Piccoli, Luca and Casiraghi, Costanza and Corti, Davide and Lanzavecchia, Antonio and Regoes, Roland R. and Loverdo, Claude and Stocker, Roman and Brumley, Douglas R. and Hardt, Wolf-Dietrich and Slack, Emma},
  year = {2017},
  month = {4},
  title = {High-avidity IgA protects the intestine by enchaining growing bacteria},
  journal = {Nature},
  publisher = {NATURE PUBLISHING GROUP},
  volume = {544},
  number = {7651},
  address = {MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND},
  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')(1-3). 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 (>= 10(8) non-motile bacteria per gram). In typical infections, much lower densities(4,5) (10(0)-10(7) 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.},
  url = {http://www.dx.doi.org/10.1038/nature22058},
  doi = {10.1038/nature22058},
  issn = {0028-0836},
}

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TY  - JOUR
AU  - Moor, Kathrin
AU  - Diard, Mederic
AU  - Sellin, Mikael E.
AU  - Felmy, Boas
AU  - Wotzka, Sandra Y.
AU  - Toska, Albulena
AU  - Bakkeren, Erik
AU  - Arnoldini, Markus
AU  - Bansept, Florence
AU  - Dal Co, Alma
AU  - Voller, Tom
AU  - Minola, Andrea
AU  - Fernandez-Rodriguez, Blanca
AU  - Agatic, Gloria
AU  - Barbieri, Sonia
AU  - Piccoli, Luca
AU  - Casiraghi, Costanza
AU  - Corti, Davide
AU  - Lanzavecchia, Antonio
AU  - Regoes, Roland R.
AU  - Loverdo, Claude
AU  - Stocker, Roman
AU  - Brumley, Douglas R.
AU  - Hardt, Wolf-Dietrich
AU  - Slack, Emma
PY  - 2017
DA  - 2017/04/27
TI  - High-avidity IgA protects the intestine by enchaining growing bacteria
JO  - Nature
VL  - 544
IS  - 7651
PB  - NATURE PUBLISHING GROUP
SN  - 0028-0836
AB  - 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')(1-3). 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 (>= 10(8) non-motile bacteria per gram). In typical infections, much lower densities(4,5) (10(0)-10(7) 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.
DO  - 10.1038/nature22058
UR  - http://www.dx.doi.org/10.1038/nature22058
ER  -