Toll-like Receptor 10 in<i>Helicobacter pylori</i>Infection

Nagashima, Hiroyuki; Iwatani, Shun; Cruz, Modesto; Abreu, José A. Jiménez; Uchida, Tomohisa; Mahachai, Varocha; Vilaichone, Ratha-Korn; Graham, David Y.; Yamaoka, Yoshio

doi:10.1093/infdis/jiv270

Cited by 89 publications

(54 citation statements)

References 46 publications

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“…In previous studies, we have confirmed our microarray data using qRT-PCR with β-actin as the housekeeping gene. In general, our results have been similar [24, 32]. The reason why the qRT-PCR results in the current study do not match that of the microarray data is unclear.…”

Section: Discussionsupporting

confidence: 53%

Autophagy‐related genes in Helicobacter pylori infection

et al. 2017

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Background In vitro studies have shown that Helicobacter pylori (H. pylori) infection induces autophagy in gastric epithelial cells. However, prolonged exposure to H. pylori reduces autophagy by preventing maturation of the autolysosome. The alterations of the autophagy-related genes in H. pylori infection are not yet fully understood. Materials and Methods We analyzed autophagy-related gene expression in H. pylori infected gastric mucosa compared with uninfected gastric mucosa obtained from 136 Bhutanese volunteers with mild dyspeptic symptoms. We also studied single nucleotide polymorphisms (SNPs) of autophagy-related gene in 283 Bhutanese participants to identify the influence on susceptibility to H. pylori infection. Results Microarray analysis of 226 autophagy-related genes showed that 16 genes were up-regulated (7%) and 9 were down-regulated (4%). We used quantitative reverse transcriptase-polymerase chain reaction to measured mRNA levels of the down-regulated genes (ATG16L1, ATG5, ATG4D and ATG9A) that were core molecules of autophagy. ATG16L1 and ATG5 mRNA levels in H. pylori positive specimens (n = 86) were significantly less than in H. pylori negative specimens (n = 50). ATG16L1 mRNA levels were inversely related to H. pylori density. We also compared SNPs of ATG16L1 (rs2241880) among 206 H. pylori-positive and 77 negative subjects. The odds ratio for the presence of H. pylori in the GG genotype was 0.40 (95% CI: 0.18-0.91) relative to the AA/AG genotypes. Conclusions Autophagy-related gene expression profiling using high-throughput microarray analysis indicated that down-regulation of core autophagy machinery genes may depress autophagy functions and possibly provide a better intracellular habit for H. pylori in gastric epithelial cells.

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Section: Discussionsupporting

confidence: 53%

Autophagy‐related genes in Helicobacter pylori infection

et al. 2017

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“…Samples from 136 subjects from Bhutan (median age, 40 years; age range, 16 to 92 years) and 157 subjects from the Dominican Republic (median age, 47 years; age range, 17 to 91 years) were included in this study (Table 1). These subjects were previously reported in studies of the effect of H. pylori infection on IL-8 and IL-10 mRNA levels (22) and TLR10 expression (23) in the gastric mucosa.…”

Section: Resultsmentioning

confidence: 55%

“…Microarray analysis was used to examine mRNA expression profiles of IL-17 ligand (IL-17A, B, C, D, E and F) and receptor (IL-17RA, RB, RC, RD, and RE) members in H. pylori-infected gastric mucosa (Table 2). We selected 32 samples (16 from Bhutan and 16 from the Dominican Republic) based on typical pathological findings (4 from H. pylori-negative normal mucosa and 12 from H. pylori-positive gastritis mucosa from each country, as described previously [23]). …”

Section: Resultsmentioning

confidence: 99%

“…We used gastric biopsy specimens obtained from subjects with mild dyspeptic symptoms living in two widely separated regions, Bhutan, in South Asia, and the Dominican Republic, a Caribbean country (22,23). Written informed consent was obtained from all participants, and the protocols were approved by the ethics committee of Oita University Faculty of Medicine (Japan), Chulalongkorn University (Thailand), and Universidad Autonoma de Santo Domingo (Dominican Republic), as well by the local hospitals where we collected gastric mucosal specimens.…”

Section: Methodsmentioning

confidence: 99%

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Interleukin-17C in Human Helicobacter pylori Gastritis

et al. 2017

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The interleukin-17 (IL-17) family of cytokines (IL-17A to IL-17F) is involved in many inflammatory diseases. Although IL-17A is recognized as being involved in the pathophysiology of Helicobacter pylori-associated diseases, the role of other IL-17 cytokine family members remains unclear. Microarray analysis of IL-17 family cytokines was performed in H. pylori-infected and uninfected gastric biopsy specimens. IL-17C mRNA was upregulated approximately 4.5-fold in H. pylori-infected gastric biopsy specimens. This was confirmed by quantitative reverse transcriptase PCR in infected and uninfected gastric mucosa obtained from Bhutan and from the Dominican Republic. Immunohistochemical analysis showed that IL-17C expression in H. pylori-infected gastric biopsy specimens was predominantly localized to epithelial and chromogranin A-positive endocrine cells. IL-17C mRNA levels were also significantly greater among cagA-positive than cagA-negative H. pylori infections (P ϭ 0.012). In vitro studies confirmed an increase in IL-17C mRNA and protein levels in cells infected with cagA-positive infections compared to cells infected with either cagA-negative or cag pathogenicity island (PAI) mutant. Chemical inhibition of IB kinase (IKK), mitogen-activated protein extracellular signal-regulated kinase (MEK), and Jun N-terminal kinase (JNK) inhibited induction of IL-17C proteins in infected cells, whereas p38 inhibition had no effect on IL-17C protein secretion. In conclusion, H. pylori infection was associated with a significant increase in IL-17C expression in human gastric mucosa. The role of IL-17C in the pathogenesis of H. pyloriinduced diseases remains to be determined.

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“…PAMPs can originate from a wide array of molecules such as lipids, nucleic acids, and specific proteins that can be derived from organisms of bacterial, viral, or fungal origin. So far there are 10 identified human TLRs, however, not all are manipulated by H. pylori ; TLR2 as a homo- or hetero-dimer with TLR1 or TLR6 (lipoteichoic acid, NapA, Hsp60), TLR4 (lipopolysaccharide), TLR5 (flagella), TLR9 (hypo-methylated DNA), and TLR10 hetero-dimerized with TLR2 (hypothesized to detect lipopolysaccharides) have been shown to interact with H. pylori (Peek et al 2010; Kim et al 2013; Nagashima et al 2015; Koch et al 2015; Pachathundikandi and Backert 2016). TLRs are an essential component of the innate immune system and are expressed both on cell surfaces and intracellularly.…”

Section: Toll-like Receptor Modulation By H Pylorimentioning

confidence: 99%

DNA Transfer and Toll-like Receptor Modulation by Helicobacter pylori

Varga

Peek

2017

Current Topics in Microbiology and Immunology

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Helicobacter pylori is the most common bacterial infection worldwide, and virtually all infected persons develop co-existing gastritis. H. pylori is able to send and receive signals from the gastric mucosa, which enables both host and microbe to engage in a dynamic equilibrium. In order to persist within the human host, H. pylori has adopted dichotomous strategies to both induce inflammation as a means of liberating nutrients while simultaneously tempering the immune response to augment its survival. Toll-like receptors (TLRs) and Nod proteins are innate immune receptors that are present in epithelial cells and represent the first line of defense against pathogens. To ensure persistence, H. pylori manipulates TLR-mediated defenses using strategies that include rendering its LPS and flagellin to be non-stimulatory to TLR4 and TLR5, respectively; translocating peptidoglycan into host cells to induce NOD1-mediated anti-inflammatory responses; and translocating DNA into host cells to induce TLR9 activation.

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Toll-like Receptor 10 inHelicobacter pyloriInfection

Cited by 89 publications

References 46 publications

Autophagy‐related genes in Helicobacter pylori infection

Autophagy‐related genes in Helicobacter pylori infection

Interleukin-17C in Human Helicobacter pylori Gastritis

DNA Transfer and Toll-like Receptor Modulation by Helicobacter pylori

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