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ATP released by intestinal bacteria limits the generation of protective IgA against enteropathogens

Title: ATP released by intestinal bacteria limits the generation of protective IgA against enteropathogens
Authors: Proietti, Michele; Perruzza, Lisa; Scribano, Daniela; Pellegrini, Giovanni; D'Antuono, Rocco; Strati, Francesco; Raffaelli, Marco; Gonzalez, Santiago F.; Thelen, Marcus; Hardt, Wolf-Dietrich; id_orcid:0 000-0002-9892-6420; Slack, Emma; Nicoletti, Mauro; Grassi, Fabio
Source: Nature Communications, 10
Publisher Information: Nature
Publication Year: 2019
Collection: ETH Zürich Research Collection
Description: T cell dependent secretory IgA (SIgA) generated in the Peyer’s patches (PPs) of the small intestine shapes a broadly diverse microbiota that is crucial for host physiology. The mutualistic co-evolution of host and microbes led to the relative tolerance of host’s immune system towards commensal microorganisms. The ATP-gated ionotropic P2X7 receptor limits T follicular helper (Tfh) cells expansion and germinal center (GC) reaction in the PPs. Here we show that transient depletion of intestinal ATP can dramatically improve high-affinity IgA response against both live and inactivated oral vaccines. Ectopic expression of Shigella flexneri periplasmic ATP-diphosphohydrolase (apyrase) abolishes ATP release by bacteria and improves the specific IgA response against live oral vaccines. Antibody responses primed in the absence of intestinal extracellular ATP (eATP) also provide superior protection from enteropathogenic infection. Thus, modulation of eATP in the small intestine can affect high-affinity IgA response against gut colonizing bacteria. ; ISSN:2041-1723
Document Type: article in journal/newspaper
File Description: application/application/pdf
Language: English
Relation: info:eu-repo/semantics/altIdentifier/wos/000455762200012; info:eu-repo/grantAgreement/SNF/Exzellenzbeitrag in Lebenswissenschaften/173338; https://hdl.handle.net/20.500.11850/320590
DOI: 10.3929/ethz-b-000320590
Availability: https://hdl.handle.net/20.500.11850/320590; https://doi.org/10.3929/ethz-b-000320590
Rights: info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ ; Creative Commons Attribution 4.0 International
Accession Number: edsbas.B0768F1C
Database: BASE