Salmonella effector driven invasion of the gut epithelium: breaking in and setting the house on fire

Salmonella Typhimurium (S.Tm) is a major cause of diarrheal disease. The invasion into intestinal epithelial cells (IECs) is a central step in the infection cycle. It is associated with gut inflammation and thought to benefit S.Tm proliferation also in the intestinal lumen. Importantly, it is still not entirely clear how inflammation is elicited and to which extent it links to IEC invasion efficiency in vivo. In this review, we summarize recent findings explaining IEC invasion by type-three-secretion system-1 (TTSS-1) effector proteins and discuss their effects on invasion and gut inflammation. In non-polarized tissue culture cells, the TTSS-1 effectors (mainly SopB/E/E2) elicit large membrane ruffles fueling cooperative invasion, and can directly trigger pro-inflammatory signaling. By contrast, in the murine gut, we observe discreet-invasion (mainly via the TTSS1 effector SipA) and a prominent pro-inflammatory role of the host?s epithelial inflammasome(s), which sense pathogen associated molecular patterns (PAMPs). We discuss why it has remained a major challenge to tease apart direct and indirect inflammatory effects of TTSS-1 effectors and explain why further research will be needed to fully determine their inflammation-modulating role(s).

Automated summary

Salmonella Typhimurium utilizes type-three-secretion system-1 effectors to invade intestinal epithelial cells and induce gut inflammation. The effects of these effectors on invasion and inflammation vary in different environments.