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

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

doi:10.1038/s41467-018-08156-z

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

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

Risultato della ricerca: Contributo in rivista › Articolo in rivista

22 Citazioni (Scopus)

Abstract

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.

Lingua originale	English
pagine (da-a)	250-261
Numero di pagine	12
Rivista	Nature Communications
Volume	10
DOI	https://doi.org/10.1038/s41467-018-08156-z
Stato di pubblicazione	Pubblicato - 2019

Keywords

Adenosine Triphosphate
Administration, Oral
Animals
Apyrase
Bacterial Proteins
Bacterial Vaccines
Biochemistry, Genetics and Molecular Biology (all)
Chemistry (all)
Disease Models, Animal
Escherichia coli
Female
Gastroenteritis
Gastrointestinal Microbiome
Germinal Center
Humans
Ileum
Immunoglobulin A, Secretory
Intestinal Mucosa
Mice
Mice, Inbred C57BL
Peyer's Patches
Physics and Astronomy (all)
Receptors, Purinergic P2X7
Salmonella Infections
Salmonella typhimurium
Shigella flexneri
T-Lymphocytes, Helper-Inducer

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Proietti, M., Perruzza, L., Scribano, D., Pellegrini, G., D’Antuono, R., Strati, F., Raffaelli, M., Gonzalez, S. F., Thelen, M., Hardt, W.-D., Slack, E., Nicoletti, M., & Grassi, F. (2019). ATP released by intestinal bacteria limits the generation of protective IgA against enteropathogens. Nature Communications, 10, 250-261. https://doi.org/10.1038/s41467-018-08156-z

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author = "Michele Proietti and Lisa Perruzza and Daniela Scribano and Giovanni Pellegrini and Rocco D{\textquoteright}Antuono and Francesco Strati and Marco Raffaelli and Gonzalez, {Santiago F.} and Marcus Thelen and Wolf-Dietrich Hardt and Emma Slack and Mauro Nicoletti and Fabio Grassi",

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AU - Proietti, Michele

AU - Perruzza, Lisa

AU - Scribano, Daniela

AU - Pellegrini, Giovanni

AU - D’Antuono, Rocco

AU - Strati, Francesco

AU - Raffaelli, Marco

AU - Gonzalez, Santiago F.

AU - Thelen, Marcus

AU - Hardt, Wolf-Dietrich

AU - Slack, Emma

AU - Nicoletti, Mauro

AU - Grassi, Fabio

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

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SN - 2041-1723

VL - 10

SP - 250

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JO - Nature Communications

JF - Nature Communications

ER -

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

Abstract

Keywords

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