Intestinal immunopathology is associated with decreased CD73-generated adenosine during lethal infection.
The ectonucleotidases CD39 and CD73 sequentially degrade the extracellular ATP pool and release immunosuppressive adenosine, thereby regulating inflammatory responses. This control is likely to be critical in the gastrointestinal tract where high levels of ATP are released in particular by commensal bacteria. The aim of this study was therefore to evaluate the involvement of the adenosinergic regulation in the intestine of mice in steady-state conditions and on acute infection with Toxoplasma gondii. We show that both conventional (Tconv) and regulatory (Treg) CD4(+) T lymphocytes express CD39 and CD73 in the intestine of naive mice. CD73 expression was downregulated during acute infection with T. gondii, leading to impaired capacity to produce adenosine. Interestingly, the expression of adenosine receptors was maintained and treatment with receptor agonists limited immunopathology and dysbiosis, suggesting that the activation of adenosine receptors may constitute an efficient approach to control intestinal inflammation associated with decreased ectonucleotidase expression.
Department of Molecular Biology, Laboratory of Immunobiology, Université Libre de Bruxelles, Gosselies, Belgium.
V
V
Francois
Department of Molecular Biology, Laboratory of Immunobiology, Université Libre de Bruxelles, Gosselies, Belgium.
H
H
Shehade
Department of Molecular Biology, Laboratory of Immunobiology, Université Libre de Bruxelles, Gosselies, Belgium.
V
V
Acolty
Department of Molecular Biology, Laboratory of Immunobiology, Université Libre de Bruxelles, Gosselies, Belgium.
N
N
Preyat
Institut de Pathologie et Génétique, Gosselies, Belgium.
P
P
Delrée
Department of Molecular Biology, Laboratory of Immunobiology, Université Libre de Bruxelles, Gosselies, Belgium.
M
M
Moser
Department of Molecular Biology, Laboratory of Immunobiology, Université Libre de Bruxelles, Gosselies, Belgium.
G
G
Oldenhove
D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001081:Apyrase / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D007410:Intestinal Diseases / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000469:parasitology; D051379:Mice; D018345:Mice, Knockout; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D043704:Receptor, Adenosine A2B / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology
D015703:Antigens, CD; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D016212:Transforming Growth Factor beta; D014212:Tretinoin; D015720:5'-Nucleotidase; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine