Abstract
The intestine not only plays a role in fundamental processes in digestion and nutrient absorption, but it also has a role in eliminating ingested pathogenic bacteria and viruses. Paneth cells, which reside at the base of small intestinal crypts, secrete α-defensins and contribute to enteric innate immunity through potent microbicidal activities. However, the relationship between food factors and the innate immune functions of Paneth cells remains unknown. Here, we examined whether short-chain fatty acids and amino acids induce α-defensin secretion from Paneth cells in the isolated crypts of small intestine. Butyric acid and leucine elicit α-defensin secretion by Paneth cells, which kills Salmonella typhimurium. We further measured Paneth cell secretion in response to butyric acid and leucine using enteroids, a three-dimensional ex vivo culture system of small intestinal epithelial cells. Paneth cells expressed short-chain fatty acid receptors, Gpr41, Gpr43, and Gpr109a mRNAs for butyric acid, and amino acid transporter Slc7a8 mRNA for leucine. Antagonists of Gpr41 and Slc7a8 inhibited granule secretion by Paneth cells, indicating that these receptor and transporter on Paneth cells induce granule secretion. Our findings suggest that Paneth cells may contribute to intestinal homeostasis by secreting α-defensins in response to certain nutrients or metabolites.
Highlights
Paneth cells, one of the small intestinal epithelial cell lineages, secrete the antimicrobial peptide α-defensin and contribute to enteric innate immunity through microbicidal activities [1,2,3]
We examined whether three kinds of short-chain fatty acids (SCFAs), acetic acid, propionic acid, and butyric acid, we examined whether kinds of SCFAs, acetic acid, acid, andsecretion butyric acid, induce First, α-defensin secretion from three
This study revealed that Paneth cells recognize bacteria and butyric acid and leucine and This that study they secrete α-defensin incells response to microbial metabolites or nutrients
Summary
One of the small intestinal epithelial cell lineages, secrete the antimicrobial peptide α-defensin and contribute to enteric innate immunity through microbicidal activities [1,2,3]. It has been reported that mouse α-defensin, cryptdin, elicits specific bactericidal activities, i.e., potent killing of pathogenic bacteria, with a lesser response against commensals [4]. The small intestinal microbiota changes in response to a difference in α-defensin levels [5]. Secreted α-defensin influences the colonic microbiota based on a previous report, which showed that α-defensin was recovered from the colonic lumen and feces [6,7]. The human intestine harbors over 1 × 1014 diverse bacteria [8]. The intestinal microbiota composition and metabolites affect host immunity; a normal intestinal microbiota is important for intestinal homeostasis
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