Apoptosis of Enterocytes: A Possible Virulence Factor of Salmonella enterica serovar Typhimurium
The gastrointestinal tract is composed of several sections including the small intestine. The large surface area of the small intestine allows for efficient nutrient absorption by enterocytes but also provides abundant points for invasion by microorganisms Paneth cells, specialized defense cells in the small intestinal mucosa, contain large amounts of antimicrobial peptides, which are released in response to various stimuli including endocrine signaling and bacterial products. Thus, to overcome this host defense barrier, pathogenic microorganisms express various virulence factors. Salmonella enterica serovar Typhimurium (ST) is able to infect a broad spectrum of hosts, including humans and mice. Previous studies in our laboratory showed that ST is able to down regulate the expression and production of antimicrobial peptides by Paneth cells in mice, which was accompanied by a reduction of antimicrobial peptide expressing Paneth cells. We hypothesized that ST induces apoptosis in Paneth cells, a host cell initiated cell suicide leading to DNA fragmentation. To show this we enumerated the number of apoptotic cells in small intestinal tissue section from infected and control mice using a TUNEL immunofluorescence assay specific for DNA fragmentation. However, we found statistically increased apoptotic signals in regions where enterocytes are located. These studies suggest that the invasion of intestinal epithelial cells during the enteric phase of infection induces apoptosis of enterocytes, thus leading to deregulation of endocrine signaling between enterocytes and Paneth cells. Ongoing studies are aimed to confirm the increased apoptosis in response to ST probing for PARP 85p fragments reflecting an earlier stage of apoptosis.