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

Proietti, Michele; Perruzza, Lisa; Scribano, Daniela; Pellegrini, Giovanni; D’Antuono, Rocco; Strati, Francesco; Raffaelli, Marco; Gonzalez, Santiago F.; Thelen, Marcus; Hardt, Wolf-Dietrich; Slack, Emma; Nicoletti, Mauro; Grassi, Fabio

doi:10.1038/s41467-018-08156-z

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Journal article

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

Proietti, Michele Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - CCI-Center for Chronic Immunodeficiency, Universitätsklinikum Freiburg, Germany
Perruzza, Lisa Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Scribano, Daniela Department of Medical and Oral Sciences and Biotechnologies, University "Gabriele D’Annunzio", Chieti, Italy - Department of Public Health and Infectious Diseases, University "La Sapienza", Rome, Italy
Pellegrini, Giovanni Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Switzerland
D’Antuono, Rocco Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Strati, Francesco Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Raffaelli, Marco Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Gonzalez, Santiago F. Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Thelen, Marcus Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Hardt, Wolf-Dietrich Institute of Microbiology, ETH Zürich, Switzerland
Slack, Emma Institute of Microbiology, ETH Zürich, Switzerland
Nicoletti, Mauro Department of Medical and Oral Sciences and Biotechnologies, University "Gabriele D’Annunzio", Chieti, Italy
Grassi, Fabio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi", Milan, Italy - Department of Medical Biotechnology and Translational Medicine (BIOMETRA), Università degli Studi di Milano, Milan, Italy

16.01.2019

Published in:

Nature Communications. - 2019, vol. 10, p. Art. number: 250

English 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 highaffinity IgA response against gut colonizing bacteria.

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