title: Ecto-5'-nucleotidase (CD73) regulates host inflammatory responses and exacerbates murine salmonellosis.
abstract: Food-borne Salmonella spp., are a major cause of hospitalization and death. Adenosine, an important immune regulator of inflammation, limits tissue damage during infection. CD39 (nucleoside triphosphate dephosphorylase) combined with ecto-5'-nucleotidase (CD73) metabolizes ATP to adenosine. We studied the expressions of CD39 and CD73 in tissues, and T helper cells in mice after Salmonella infection and evaluated the role of CD73 in regulating immune responses and bacterial clearance in wild-type and CD73-deficient (CD73(-/-)) mice. Both CD39 and CD73 transcript levels declined in the infected wild-type mice. Compared to wild-type mice, tissues from infected CD73(-/-) mice had significantly higher expression of pro-inflammatory cytokines and reduced anti-inflammatory responses. CD73(-/-) mice were more resistant to infection and had a greater inflammatory responses and a significantly lower bacterial load in the liver compared to wild-type mice. Thus, CD73 expression attenuates inflammation during murine Salmonellosis and impairs immunity, leading to increased bacterial colonization and prolonged infection.
authors.affiliation: Immunobiology Branch, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD 20708.
authors.forename: M Samiul
authors.initials: MS
authors.lastname: Alam
authors.affiliation: Immunobiology Branch, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD 20708.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Kuo
authors.affiliation: Division of Comparative Pathology and Medicine, University of California, San Diego, 9500 Gilman Drive, MC 0612, San Diego, CA 92093-0612.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Ernst
authors.affiliation: Division of Comparative Pathology and Medicine, University of California, San Diego, 9500 Gilman Drive, MC 0612, San Diego, CA 92093-0612.
authors.forename: Victoria
authors.initials: V
authors.lastname: Derr-Castillo
authors.affiliation: Immunobiology Branch, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD 20708.
authors.forename: Marion
authors.initials: M
authors.lastname: Pereira
authors.affiliation: Immunobiology Branch, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD 20708.
authors.forename: Dennis
authors.initials: D
authors.lastname: Gaines
authors.affiliation: Immunobiology Branch, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD 20708.
authors.forename: Matthew
authors.initials: M
authors.lastname: Costales
authors.affiliation: Immunobiology Branch, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD 20708.
authors.forename: Elmer
authors.initials: E
authors.lastname: Bigley
authors.affiliation: Immunobiology Branch, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD 20708.
authors.forename: Kristina
authors.initials: K
authors.lastname: Williams
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001081:Apyrase / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004789:Enzyme Activation; D017353:Gene Deletion; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D018836:Inflammation Mediators / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D018836:Inflammation Mediators; D015720:5'-Nucleotidase; D001081:Apyrase; C067869:CD39 antigen