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- W1557547567 abstract "Previous work has shown that adenosine is a key mediator of bacterial-epithelial cell interactions. CD73 is an ecto-5'-nucleotidase expressed abundantly on the apical surface of intestinal epithelial cells (IEC) that catalyzes the conversion of 5’-adenosine monophosphate (AMP) to adenosine (Ado). Here, we hypothesized that CD73 activity is important in invasion of IECs by the enteric pathogen Salmonella typhimurium. In this work, we demonstrate that pharmacologic inhibition of CD73 activity and lentiviral-mediated knockdown of CD73 expression significantly attenuated Ado production by cultured T84 human colonic epithelial cells (approximately 7-fold reduction in the ability to convert etheno-AMP to etheno-Ado). Furthermore, inhibition of CD73 activity by these two methods diminished invasion of T84 cells by Salmonella typhimurium. Based on these in vitro data, a transgenic mouse was generated with IEC-specific knockout of CD73 (CD73f/f x Villin-Cre). These CD73 tissue-specific knockout mice were protected in an S. typhimurium model of infectious colitis compared to control animals. IEC-specific knockout animals revealed attenuated weight loss and diminished histopathological severity of colitis at 24 and 48 hours after infection. Correspondingly, there was a significant decrease in disseminated bacteria isolated from mesenteric lymph nodes and spleen, demonstrating attenuated bacterial invasion in the absence of CD73. In conclusion, these results demonstrate that CD73 is a key regulator of infection by the enteric invasive pathogen S. typhimurium and implicates a prominent role for extracellular adenosine in Salmonella interactions with IEC. Grant Funding Source: Supported by NIH and CCFA" @default.
- W1557547567 created "2016-06-24" @default.
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- W1557547567 date "2014-04-01" @default.
- W1557547567 modified "2023-09-27" @default.
- W1557547567 title "Intestinal epithelial ecto‐5’‐nucleotidase CD73 regulates invasion by Salmonella typhimurium (488.4)" @default.
- W1557547567 doi "https://doi.org/10.1096/fasebj.28.1_supplement.488.4" @default.
- W1557547567 hasPublicationYear "2014" @default.
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