Salmonella Typhimurium diarrhea: switching the mucosal epithelium from homeostasis to defense

The mammalian intestine is a complex biological system composed of the epithelium, the gut associated immune system, a commensal microbial community of approx. 1010 cells per gram of content (‘microbiota’) and an occasional onslaught by pathogens. The mechanisms governing homeostasis and immune defense are of great importance, but incompletely understood. This is explained by the system's sheer complexity. So far, no single study has considered all relevant parameters, that is (i) innate and adaptive mucosal immune responses; (ii) mucosa cell gene expression; (iii) community composition of the microbiota; (iv) microbiota gene expression; (v) genetic profiling of the host; (vi) the virulence complement expressed by the pathogen in vivo. This exquisite complexity explains why simplified model systems have fuelled much recent progress on the system's regulating principles. Here, we focus on one particular model, the streptomycin pretreated mouse model for Salmonella diarrhea, to illustrate novel concepts in microbe–mucosa interaction, that is how this system switches from homeostasis to disease.

► Activation of homeostatic gut epithelium. ► Signal amplification by neighboring cell activation. ► Actively triggering inflammation via caspase-1/IL-1/IL-18.