Diet dependent, microbiota independent regulation of IL 10 producing lamina propria macrophages in the small intestine
Intestinal resident macrophages (Mphs) regulate gastrointestinal homeostasis via production of an anti inflammatory cytokine interleukin (IL) 10. Although a constant replenishment by circulating monocytes is required to maintain the pool of resident Mphs in the colonic mucosa, the homeostatic regulation of Mph in the small intestine (SI) remains unclear. Here, we demonstrate that direct stimulation by dietary amino acids regulates the homeostasis of intestinal Mphs in the SI. Mice that received total parenteral nutrition (TPN) which deprives the animals of enteral nutrients, displayed a significant decrease of IL 10 producing Mphs in the SI, whereas the IL 10 producing CD4+ T cells remained intact. Likewise, enteral nutrient deprivation selectively affected the monocyte derived F4/80+ Mph population, but not non monocytic precursor derived CD103+ dendritic cells. Notably, in contrast to colonic Mphs, the replenishment of SI Mphs and their IL 10 production were not regulated by the gut microbiota. Rather, SI Mphs were directly regulated by dietary amino acids. Collectively, our study highlights the diet dependent, microbiota independent regulation of IL 10 producing resident Mphs in the SI.
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