Toll-like receptor 9 expressed in proximal intestinal enteroendocrine cells detects bacteria resulting in secretion of cholecystokinin

Toll-like receptors (TLRs) play a key role in the recognition of microbes via detection of specific and conserved microbial molecular features. TLRs, mainly expressed in immune cells, interact with intestinal microbiome. Little is known about mechanism(s) of sensing of bacteria by the intestinal sur...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2020-05, Vol.525 (4), p.936-940
Main Authors: Daly, K., Burdyga, G., Al-Rammahi, M., Moran, A.W., Eastwood, C., Shirazi-Beechey, S.P.
Format: Article
Language:English
Subjects:
Animals
Bacteria
Cell Line
Cholecystokinin
Cholecystokinin - metabolism
Enteroendocrine cell
Enteroendocrine Cells - metabolism
Enteroendocrine Cells - microbiology
Female
Genome, Bacterial
Gut sensing
Host-Pathogen Interactions - physiology
Intestines - cytology
Male
Mice, Inbred C57BL
Swine
TLR9
Toll-Like Receptor 9 - metabolism
Toll-Like Receptors - metabolism
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Summary:Toll-like receptors (TLRs) play a key role in the recognition of microbes via detection of specific and conserved microbial molecular features. TLRs, mainly expressed in immune cells, interact with intestinal microbiome. Little is known about mechanism(s) of sensing of bacteria by the intestinal surface enteroendocrine cells (EECs). We show here that TLR9 is expressed by the EECs of proximal intestine in a range of species and is co-expressed with the satiety hormone cholecystokinin (CCK). CCK secreted in excess induces emesis (vomiting). Using an EEC model cell line, STC-1, we demonstrate that in response to the TLR9 agonist, DNA containing unmethylated CpG dinucleotide motifs, STC-1 cells secrete CCK and that this secretion is inhibited by specific inhibitors of TLR9. Exposure of STC-1 cells to heat-inactivated pathogenic bacteria, Escherichia coli O55/H7, Shigella flexneri 2457T, Salmonella typhimurium ST4/74, and non-pathogenic Lactobacillus amylovorus GRL1112, results to an increase in CCK secretion compared to untreated control. The magnitudes of CCK release are higher in response to pathogenic bacteria and lowest in response to the non-pathogenic L. amylovorus. The pathogenic strains not only have substantially bigger genomes than L. amylovorus, they also have significantly higher numbers/frequency of RR/CG/YY stimulatory CpG hexamers in their genomic DNA. Pathogen-induced excessive secretion of the gut hormone CCK, provoking emesis can serve as a protective mechanism against development of enteric infections. •TLR9 is expressed in proximal intestinal enteroendocrine cells.•TLR9 recognition of pathogenic bacteria evokes secretion of cholecystokinin.•The gut hormone cholecystokinin if secreted in excess induces emesis.•This can serve as a protective mechanism against development of enteric infections.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2020.02.163