Abstract
Background Salmonella infection is a common public health problem that can become chronic and increase the risk of inflammatory bowel diseases and cancer. AvrA is a Salmonella bacterial type III secretion effector protein. Increasing evidence demonstrates that AvrA is a multi-functional enzyme with critical roles in inhibiting inflammation, regulating apoptosis, and enhancing proliferation. However, the chronic effects of Salmonella and effector AvrA in vivo are still unknown. Moreover, alive, mutated, non-invasive Salmonella is used as a vector to specifically target cancer cells. However, studies are lacking on chronic infection with non-pathogenic or mutated Salmonella in the host.Methods/Principal FindingsWe infected mice with Salmonella Typhimurium for 27 weeks and investigated the physiological effects as well as the role of AvrA in intestinal inflammation. We found altered body weight, intestinal pathology, and bacterial translocation in spleen, liver, and gallbladder in chronically Salmonella-infected mice. Moreover, AvrA suppressed intestinal inflammation and inhibited the secretion of cytokines IL-12, IFN-γ, and TNF-α. AvrA expression in Salmonella enhanced its invasion ability. Liver abscess and Salmonella translocation in the gallbladder were observed and may be associated with AvrA expression in Salmonella.Conclusion/SignificanceWe created a mouse model with persistent Salmonella infection in vivo. Our study further emphasizes the importance of the Salmonella effector protein AvrA in intestinal inflammation, bacterial translocation, and chronic infection in vivo.
Highlights
Salmonellosis is one of the most common enteric infections in the United States
To determine whether AvrA is responsible for the chronic intestinal inflammation, we focused on bacterial strains with parental PhoPc, PhoPc AvrA mutant (AvrA2), and PhoPc AvrA2 with a complemented plasmid encoding AvrA (PhoPc AvrA2/ AvrA+) in vivo, as we used in previous studies [20,21,22,24,25]
Many researchers have taken advantage of the colitis induced by Salmonella Typhimurium to study the early phase of inflammation and infection
Summary
In addition to the public health concern of Salmonella outbreaks, Salmonella colonization and infection can be chronic [1] and increase the risk of other gastrointestinal (GI) diseases, including chronic inflammation and gallbladder cancer [2,3]. A recent population-based cohort study demonstrates an increased risk of inflammatory bowel diseases in individuals with Salmonella infection [2]. There have been no studies on chronic infection with non-pathogenic or mutated Salmonella in the host. Salmonella infection is a common public health problem that can become chronic and increase the risk of inflammatory bowel diseases and cancer. The chronic effects of Salmonella and effector AvrA in vivo are still unknown. Studies are lacking on chronic infection with non-pathogenic or mutated Salmonella in the host
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