Salmonella Gut Invasion Involves TTSS-2-Dependent Epithelial Traversal, Basolateral Exit, and Uptake by Epithelium-Sampling Lamina Propria Phagocytes

Abstract

Salmonella Typhimurium causes diarrhea by infecting the epithelium and lamina propria of the intestinal mucosa and by secreting various effector proteins through type III secretion systems (TTSSs). However, the mechanisms by which Salmonella transverses the epithelium and is subsequently released into the lamina propria are poorly understood. Using a murine Salmonella-diarrhea model and in vivo microscopy, we show that epithelial traversal requires TTSS-1-mediated invasion and TTSS-2-dependent trafficking to the basolateral side. After being released into the lamina propria, the bacterium is transiently extracellular before being taken up by phagocytes, including CD11c(+)CX(3)CR1(high) monocytic phagocytes (MPs), which were found to constitutively sample cellular material shed from the basolateral side of the epithelium. Thus, Salmonella infects the cecal mucsa through a step-wise process wherein the bacterium transverses the epithelium through TTSS-2-dependent trafficking and then likely exploits lamina propria MPs, which are sampling the epithelium, to enter and replicate within the host.

Concepts and Mechanisms: Crossing Host Barriers

“…S. Typhimurium may also cross the intestinal barrier through the epithelial cells in an SPI-1 dependent manner. Recently, the mechanism by which S. Typhimurium crosses the epithelial barrier at the cecal level and is released in the lamina propria has been studied in detail (Muller et al 2012). It has been shown by use of in vivo confocal microscopy in a murine Salmonella-diarrhea model that the breaching of the epithelial barrier relies on both TTSS-1-mediated invasion and TTSS-2-dependent transcytosis to the basolateral side.…”

No Protective Effects of High-Dosage Dietary Zinc Oxide on Weaned Pigs Infected with Salmonella enterica Serovar Typhimurium DT104

“…For this reason, S. Typhimurium could escape the lysis mechanisms applied by host immune cells (42) by hiding itself in host cells, because the host cells, especially dendritic cells, are no longer able to present Salmonella antigens through MHC II molecules to the T helper cells. This mechanism could explain our findings that the relative percentages of CD2 ϩ T and NK cells and of CD4…”

The Salmonella Spi1 Virulence Regulatory Protein HilD Directly Activates Transcription of the Flagellar Master OperonflhDC

“…Spi1 is needed for the invasion of the intestinal epithelium leading to gastroenteritis (7,8), while Spi2 plays a role during trafficking to the basolateral side of epithelial cells (9) and during later Salmonella replication and survival within macrophages (10,11). Both systems are regulated in a spatial and temporal manner to ensure the production of gene products at the correct points during infection.…”