Toll-like Receptor 10 in Helicobacter pylori Infection

Innate immunity plays important roles in the primary defense against pathogens, and epidemiological studies have suggested a role for Toll-like receptor 1 (TLR1) in Helicobacter pylori susceptibility. Microarray analysis of gastric biopsy specimens from H. pylori-positive and uninfected subjects sho...

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Veröffentlicht in:The Journal of infectious diseases 2015-11, Vol.212 (10), p.1666-1676
Hauptverfasser: Nagashima, Hiroyuki, Iwatani, Shun, Cruz, Modesto, Jiménez Abreu, José A., Uchida, Tomohisa, Mahachai, Varocha, Vilaichone, Ratha-korn, Graham, David Y., Yamaoka, Yoshio
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container_end_page 1676
container_issue 10
container_start_page 1666
container_title The Journal of infectious diseases
container_volume 212
creator Nagashima, Hiroyuki
Iwatani, Shun
Cruz, Modesto
Jiménez Abreu, José A.
Uchida, Tomohisa
Mahachai, Varocha
Vilaichone, Ratha-korn
Graham, David Y.
Yamaoka, Yoshio
description Innate immunity plays important roles in the primary defense against pathogens, and epidemiological studies have suggested a role for Toll-like receptor 1 (TLR1) in Helicobacter pylori susceptibility. Microarray analysis of gastric biopsy specimens from H. pylori-positive and uninfected subjects showed that TLR10 messenger RNA (mRNA) levels were upregulated approximately 15-fold in infected subjects; these findings were confirmed by real-time quantitative polymerase chain reaction analysis. Immunohistochemical investigation showed increased TLR10 expression in the gastric epithelial cells of infected individuals. When H. pylori was cocultured with NCI-N87 gastric cells, both TLR10 and TLR2 mRNA levels were upregulated. We compared the ability of TLR combinations to mediate nuclear factor-kB (NF-kB) activation. Compared with other TLR2 subfamily heterodimers, the TLR2/TLR10 heterodimer mediated the greatest NF-kB activation following exposure to heat-killed H. pylori or H. pylori lipopolysaccharide. We conclude that TLR10 is a functional receptor involved in the innate immune response to H. pylori infection and that the TLR2/TLR10 heterodimer functions in H. pylori lipopolysaccharide recognition.
doi_str_mv 10.1093/infdis/jiv270
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Microarray analysis of gastric biopsy specimens from H. pylori-positive and uninfected subjects showed that TLR10 messenger RNA (mRNA) levels were upregulated approximately 15-fold in infected subjects; these findings were confirmed by real-time quantitative polymerase chain reaction analysis. Immunohistochemical investigation showed increased TLR10 expression in the gastric epithelial cells of infected individuals. When H. pylori was cocultured with NCI-N87 gastric cells, both TLR10 and TLR2 mRNA levels were upregulated. We compared the ability of TLR combinations to mediate nuclear factor-kB (NF-kB) activation. Compared with other TLR2 subfamily heterodimers, the TLR2/TLR10 heterodimer mediated the greatest NF-kB activation following exposure to heat-killed H. pylori or H. pylori lipopolysaccharide. We conclude that TLR10 is a functional receptor involved in the innate immune response to H. pylori infection and that the TLR2/TLR10 heterodimer functions in H. pylori lipopolysaccharide recognition.</description><identifier>ISSN: 0022-1899</identifier><identifier>EISSN: 1537-6613</identifier><identifier>DOI: 10.1093/infdis/jiv270</identifier><identifier>PMID: 25977263</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Cell Line ; Coculture Techniques ; Epithelial Cells - chemistry ; Gastric Mucosa - pathology ; Gene Expression Profiling ; Helicobacter Infections - immunology ; Helicobacter pylori - immunology ; Humans ; Immunohistochemistry ; Lipopolysaccharides - immunology ; Major and Brief Reports ; Microarray Analysis ; NF-kappa B - analysis ; PATHOGENESIS AND HOST RESPONSE ; Real-Time Polymerase Chain Reaction ; Toll-Like Receptor 10 - genetics ; Toll-Like Receptor 10 - metabolism ; Up-Regulation</subject><ispartof>The Journal of infectious diseases, 2015-11, Vol.212 (10), p.1666-1676</ispartof><rights>Copyright © 2015 Oxford University Press on behalf of the Infectious Diseases Society of America</rights><rights>The Author 2015. 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Microarray analysis of gastric biopsy specimens from H. pylori-positive and uninfected subjects showed that TLR10 messenger RNA (mRNA) levels were upregulated approximately 15-fold in infected subjects; these findings were confirmed by real-time quantitative polymerase chain reaction analysis. Immunohistochemical investigation showed increased TLR10 expression in the gastric epithelial cells of infected individuals. When H. pylori was cocultured with NCI-N87 gastric cells, both TLR10 and TLR2 mRNA levels were upregulated. We compared the ability of TLR combinations to mediate nuclear factor-kB (NF-kB) activation. Compared with other TLR2 subfamily heterodimers, the TLR2/TLR10 heterodimer mediated the greatest NF-kB activation following exposure to heat-killed H. pylori or H. pylori lipopolysaccharide. 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subjects Cell Line
Coculture Techniques
Epithelial Cells - chemistry
Gastric Mucosa - pathology
Gene Expression Profiling
Helicobacter Infections - immunology
Helicobacter pylori - immunology
Humans
Immunohistochemistry
Lipopolysaccharides - immunology
Major and Brief Reports
Microarray Analysis
NF-kappa B - analysis
PATHOGENESIS AND HOST RESPONSE
Real-Time Polymerase Chain Reaction
Toll-Like Receptor 10 - genetics
Toll-Like Receptor 10 - metabolism
Up-Regulation
title Toll-like Receptor 10 in Helicobacter pylori Infection
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