Salmonella survives 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 of Salmonella enterica serovar Typhimurium within macrophages stimulated with TLR ligands is poorly understood. We studied the infection dynamics of Salmonella in murine macrophages previously exposed to TLR ligands and report that treatment of macrophages with four different TLR agonists resulted in their increased phagocytic capacity toward Salmonella but not fluorescent microspheres. Further analysis revealed that the intracellular replication of Salmonella was enhanced in TLR-stimulated macrophages in a manner requiring a functional type III secretion system and enhanced transcriptional activity of the sseA virulence gene operon. Studies of mice that normally resolve an acute primary infection with Salmonella revealed that pretreatment of animals with CpG DNA had a detrimental effect on disease outcome. CpG-treated mice infected with Salmonella all succumbed to infection and had higher bacterial loads in the spleen than did control animals. These data suggest that Salmonella can exploit macrophages activated via the innate immune system for increased intracellular survival.
Michael G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences, McMaster University, Health Sciences Centre, Room 4H17, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada.
