title: Extracellular adenosine generation in the regulation of pro-inflammatory responses and pathogen colonization.
abstract: Adenosine, an immunomodulatory biomolecule, is produced by the ecto-enzymes CD39 (nucleoside triphosphate dephosphorylase) and CD73 (ecto-5'-nucleotidase) by dephosphorylation of extracellular ATP. CD73 is expressed by many cell types during injury, infection and during steady-state conditions. Besides host cells, many bacteria also have CD39-CD73-like machinery, which helps the pathogen subvert the host inflammatory response. The major function for adenosine is anti-inflammatory, and most recent research has focused on adenosine's control of inflammatory mechanisms underlying various autoimmune diseases (e.g., colitis, arthritis). Although adenosine generated through CD73 provides a feedback to control tissue damage mediated by a host immune response, it can also contribute to immunosuppression. Thus, inflammation can be a double-edged sword: it may harm the host but eventually helps by killing the invading pathogen. The role of adenosine in dampening inflammation has been an area of active research, but the relevance of the CD39/CD73-axis and adenosine receptor signaling in host defense against infection has received less attention. Here, we review our recent knowledge regarding CD73 expression during murine Salmonellosis and Helicobacter-induced gastric infection and its role in disease pathogenesis and bacterial persistence. We also explored a possible role for the CD73/adenosine pathway in regulating innate host defense function during 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, USA. Mohammad.alam@fda.hhs.gov.
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, USA. matthew.costales@gmail.com.
authors.forename: Matthew G
authors.initials: MG
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, USA. Christopher.Cavanaugh@fda.hhs.gov.
authors.forename: Christopher
authors.initials: C
authors.lastname: Cavanaugh
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, USA. Kristina.Williams@fda.hhs.gov.
authors.forename: Kristina
authors.initials: K
authors.lastname: Williams
mesh_terms: 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; D016481:Helicobacter Infections / Q000276:immunology*; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D051379:Mice; D012480:Salmonella Infections / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D015720:5'-Nucleotidase; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine