Extracellular Adenosine Generation in the Regulation of Pro-Inflammatory Responses and Pathogen Colonization
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
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Author to whom correspondence should be addressed.
†
Current address: Department of Chemistry, The Scripps Research Institute, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USA
Academic Editor: Ivana Vancurova
Biomolecules 2015, 5(2), 775-792; https://doi.org/10.3390/biom5020775
Received: 11 March 2015
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Revised: 23 April 2015
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Accepted: 25 April 2015
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Published: 5 May 2015
(This article belongs to the Special Issue Transcriptional Regulation of Pro-Inflammatory Genes)
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.
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Keywords:
adenosine; CD39; CD73; adenosine receptors; immune response; lymphocytes; macrophage; bacterial-persistence; inflammation; cytokine
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MDPI and ACS Style
Alam, M.S.; Costales, M.G.; Cavanaugh, C.; Williams, K. Extracellular Adenosine Generation in the Regulation of Pro-Inflammatory Responses and Pathogen Colonization. Biomolecules 2015, 5, 775-792. https://doi.org/10.3390/biom5020775
AMA Style
Alam MS, Costales MG, Cavanaugh C, Williams K. Extracellular Adenosine Generation in the Regulation of Pro-Inflammatory Responses and Pathogen Colonization. Biomolecules. 2015; 5(2):775-792. https://doi.org/10.3390/biom5020775
Chicago/Turabian StyleAlam, M. S., Matthew G. Costales, Christopher Cavanaugh, and Kristina Williams. 2015. "Extracellular Adenosine Generation in the Regulation of Pro-Inflammatory Responses and Pathogen Colonization" Biomolecules 5, no. 2: 775-792. https://doi.org/10.3390/biom5020775
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