GHI special seminar: What role does the immune system play in controlling the intestinal microbiota?

Our guts are home to a complex, dense and dynamic consortia of microbes, which can have a profound impact on our health. How have we evolved to promote species and microbial functions that are beneficial, while minimizing the risk from common opportunistic pathogens such as Salmonella and E.coli? Clearly the physiology of the intestinal tract, including motility and secretions, is a key determinant of microbiota health. Our work focuses on how intestinal immunity interacts with physiology of both the host and the microbes to manipulate microbiota composition and function (1, 2). This reveals the potential for oral vaccine-based interventions that may enable more robust prophylaxis of bacterial infections (3), as well as rational microbiota engineering.

1. High-avidity IgA protects the intestine by enchaining growing bacteria. Moor K, Diard M, Sellin ME, Felmy B, Wotzka SY, Toska A, Bakkeren E, Arnoldini M, Bansept F, Dal Co A, Völler T, Minola A, Fernandez-Rodriguez B, Agatic G, Barbieri S, Piccoli L, Casiraghi C, Corti D, Lanzavecchia A, Regoes RR, Loverdo C, Stocker R, Brumley* DR, Hardt* W-D, Slack* E. 2017. Nature 544:498–502 doi:10.1038/nature22058
2. Inflammation boosts bacteriophage transfer between Salmonella. Diard M, Bakkeren E, Cornuault JK, Moor K, Hausmann A, Sellin ME, Loverdo C, Aertsen A, Ackermann M, De Paepe M, Slack E, Hardt W-D. 2017. Science355:1211-1215, doi:10.1126/science.aaf8451 
3. A rationally designed oral vaccine induces immunoglobulin A in the murine gut that directs the evolution of attenuated Salmonella variants.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, Mezzeng R, Holst O, Meier BH, Hardt WD, Slack E. Nat Microbiol. 2021 May 27. doi:10.1038/s41564-021-00911-1.