Trichomonas associated protection against Salmonella infection

Abstract

Abstract Colonization resistance (CR), defined as the ability of intestinal microbiota and host defenses to protect against pathogens, is the first line defense against intestinal infection. In our studies of innate immune recognition of intestinal Salmonella, we discovered Naip5−/− and Rag1−/− mice harbor microbiota that protect mice against Salmonella infection, which is associated with intestinal colonization by Tritrichomonas muris (Tm). Tm is a protozoon commonly found in laboratory, pet shop and wild mice, which has no definitive disease association. Recent studies have demonstrated Tm and other intestinal parasites are sensed by tastant receptors expressed by specialized intestinal tuft cells, which enhances intestinal barrier by tuft cell and goblet cell hyperlasia. Helminths and protozoa have been associated with changes in the intestinal microbiota, suggesting that intestinal protozoa may produce biologically significant alterations in the composition of gut bacteria. We demonstrate that Tm colonization of mice is associated with decreased inflammation in the intestine during Salmonella infection of streptomycin pretreated mice. Tm colonization is also associated with increased resistance to Salmonella infection and CR. Finally, we demonstrate that Tm colonized mice have an altered gut microbiome, suggesting that Tm cultivates a protective microbiome that helps prevent Salmonella colonization and infection. Our studies indicate that intestinal protozoa may influence the complex environment within the gut to help limit Salmonella invasion of the gut ecosystem and Salmonella induced intestinal inflammation, and provide insight into novel strategies that may help prevent Salmonella infection and transmission.