If one were to ask, “What happens when Salmonella infects the gut?” it might not be obvious that you’d also need to ask, “What time is it?” But indeed you’d need to know the latter to appropriately address the former. An invading Salmonella, intent on setting up camp, is trying to pitch its tent on a landscape that is changing throughout the day. The mammalian gut, like most eukaryotic and some prokaryotic cells, uses an internal timing device to control its physiological functions. The circadian, or 24-h (circa diem, about a day) clock employs an endogenous oscillator to control gene expression, metabolism, and other cellular processes in such a way that individual genes, pathways, and their components ebb and flow in activity with distinctive daily programs, meshing together to execute the enterprise of the cell. Among circadian regulated processes are aspects of the immune system, including components of the inflammatory response. Included are changes in the expression of several inflammation-related (“proinflammatory”) cytokines by macrophages not only in the animal but also ex-vivo. Not coincidentally, Salmonella thrives in the inflamed gut.
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