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



Daly, K ORCID: 0000-0002-1075-1831, Burdyga, G, Al-Rammahi, M ORCID: 0000-0002-0165-7990, Moran, AW ORCID: 0000-0003-0031-2154, Eastwood, C and Shirazi-Beechey, SP
(2020) Toll-like receptor 9 expressed in proximal intestinal enteroendocrine cells detects bacteria resulting in secretion of cholecystokinin. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 525 (4). pp. 936-940.

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: Bacteria, Gut sensing, TLR9, Enteroendocrine cell, Cholecystokinin
Depositing User: Symplectic Admin
Date Deposited: 03 Mar 2020 16:56
Last Modified: 18 Jan 2023 23:59
DOI: 10.1016/j.bbrc.2020.02.163
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3077612