Infection and Immunity
Infection and Immunity
5 years ago

Intestinal epithelial ecto-5' -nucleotidase (CD73) regulates intestinal colonization and infection by nontyphoidal Salmonella.

Saeedi BJ, Vázquez-Torres A, Burney KM, Kominsky DJ, Dobrinskikh E, Kao DJ, Colgan SP, Battista KD, Kitzenberg D
Ecto-5' -nucleotidase (CD73) is expressed abundantly on the apical surface of intestinal epithelial cells (IEC) and functions as the terminal enzyme in the generation of extracellular adenosine. Previous work has demonstrated that adenosine signaling in IECs results in a number of tissue-protective effects during inflammation; however, a rationale for its apical expression has been lacking. We hypothesized that the highly polarized expression of CD73 is indicative of an important role for extracellular adenosine as a mediator of host-microbe interactions. We show that adenosine harbors bacteriostatic activity against Salmonella enterica serovar Typhimurium that is not shared by the related purine metabolites 5' -adenosine monophosphate, inosine, or hypoxanthine. Analysis of Salmonella colonization in IEC-specific CD73 knockout mice (CD73f/f VillinCre ) revealed a nearly 10-fold increase in colonization compared to controls. Despite increased luminal colonization by Salmonella, CD73f/f VillinCre mice were protected against Salmonella colitis and reduced Salmonella burden in viscera, suggesting that adenosine promotes dissemination. Knockdown of CD73 expression in cultured IECs resulted in dramatic defects in intraepithelial localization and replication as well as defective transepithelial translocation by Salmonella In conclusion, we define a novel antimicrobial activity of adenosine in the gastrointestinal tract and unveil an important role for adenosine as a regulator of host-microbe interactions. These findings have broad implications for the development of new therapeutic agents for infectious disease.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28717030

DOI: PubMed:28717030

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.