Validating Salmonella typhimurium virulence modulation by ecto-5'-nucleotidase (CD73) in intestinal epithelial cells

Abstract

Extracellular ATP is a pro-inflammatory molecule released during intestinal insult and must be converted to adenosine by ecto-5'-nucleotidase (CD73) for the resolution of intestinal inflammation [1]. Along with its anti-inflammatory role in the intestinal mucosa, CD73-generated adenosine contributes to host-microbe interactions at the mucosal surface by modulating pathogen replication and virulence, including that of Salmonella enterica serovar Typhimurium (S. Typhimurium) [2], [3]. It has been shown, in the absence of intestinal epithelial cell-specific CD73, S. Typhimurium virulence is attenuated in vivo and in vitro, implicating the intestinal epithelium as an underappreciated source for the development of novel antimicrobial therapies. Since direct modulation of extracellular adenosine leads to pleiotropic effects, the aim of this research was to determine the mechanism(s) of S. Typhimurium virulence modulation by CD73 in intestinal epithelial cells to identify specific molecular targets that modulate pathogenesis [4], [5]