Type III secretion system-mediated immune modulation by enteropathogenic bacteria

Abstract

EPEC/EHEC, Yersinia, Salmonella and Shigella are four major enteropathogenic bacteria species that cause gastrointestinal disease using a type III secretion system (T3SS). The T3SS complex forms a needle that injects bacterial effector proteins into host cells. T3SS effectors modulate cellular functions to the bacterium’s own advantage. T3SS effectors interfere with the intestinal immune system to prevent eradication and establish enteric infection. Enteropathogenic bacteria encounter intestinal epithelial cells, phagocytic immune cells and cells of the adaptive immune system during the course of an infection. The enteropathogenic bacterial species have each developed a strategy to modulate the immune function of these cell types. While EPEC/EHEC and Yersinia actively prevent intestinal epithelial cell inflammation and phagocytic uptake, Salmonella and Shigella exploit inflammation and phagocytic cells to spread. These virulence strategies are carried out by a species-specific set of T3SS effectors. T3SS effectors have a variety of functions, but often share cellular targets, like the pro-inflammatory transcription factor NF-κB and regulators of cytoskeletal rearrangements. T3SS effector proteins are extensively adapted to a host cell specific virulence function. Together, the set of injected T3SS effectors manipulate the host’s immune response to promote bacterial survival, for each species in a unique manner.