<i>Salmonella enterica</i>Serovar Typhimurium Exploits Toll-Like Receptor Signaling during the Host-Pathogen Interaction

ABSTRACTSalmonellasurvives and replicates in host cells by using a type III secretion system to evade host immune defenses. The innate immune system plays an important role as a first line of defense against pathogens and is mediated in part by Toll-like receptors (TLRs); however, the infection dynamics ofSalmonella entericaserovar Typhimurium within macrophages stimulated with TLR ligands is poorly understood. We studied the infection dynamics ofSalmonellain murine macrophages previously exposed to TLR ligands and report that treatment of macrophages with four different TLR agonists resulted in their increased phagocytic capacity towardSalmonellabut not fluorescent microspheres. Further analysis revealed that the intracellular replication ofSalmonellawas enhanced in TLR-stimulated macrophages in a manner requiring a functional type III secretion system and enhanced transcriptional activity of thesseAvirulence gene operon. Studies of mice that normally resolve an acute primary infection withSalmonellarevealed that pretreatment of animals with CpG DNA had a detrimental effect on disease outcome. CpG-treated mice infected withSalmonellaall succumbed to infection and had higher bacterial loads in the spleen than did control animals. These data suggest thatSalmonellacan exploit macrophages activated via the innate immune system for increased intracellular survival.

Salmonella entericaSerovar Typhimurium Exploits Toll-Like Receptor Signaling during the Host-Pathogen Interaction Journal Articles