MicroRNA Modulation of Host Immune Response and Inflammation Triggered by Helicobacter pylori

Abstract

Helicobacter pylori (H. pylori) remains the most-researched etiological factor for gastric inflammation and malignancies. Its evolution towards gastric complications is dependent upon host immune response. Toll-like receptors (TLRs) recognize surface and molecular patterns of the bacterium, especially the lipopolysaccharide (LPS), and act upon pathways, which will finally lead to activation of the nuclear factor-kappa B (NF-kB), a transcription factor that stimulates release of inflammatory cytokines. MicroRNAs (MiRNAs) finely modulate TLR signaling, but their expression is also modulated by activation of NF-kB-dependent pathways. This review aims to focus upon several of the most researched miRNAs on this subject, with known implications in host immune responses caused by H. pylori, including let-7 family, miRNA-155, miRNA-146, miRNA-125, miRNA-21, and miRNA-221. TLR–LPS interactions and their afferent pathways are regulated by these miRNAs, which can be considered as a bridge, which connects gastric inflammation to pre-neoplastic and malignant lesions. Therefore, they could serve as potential non-invasive biomarkers, capable of discriminating H. pylori infection, as well as its associated complications. Given that data on this matter is limited in children, as well as for as significant number of miRNAs, future research has yet to clarify the exact involvement of these entities in the progression of H. pylori-associated gastric conditions.

Differential Expression of Tissular miRNA-155 in Pediatric Gastritis

“…MiRNAs are among the molecules with an expression change that is very sensitive to microscopic alteration of gastric mucosal integrity. Most studies have, so far, investigated their behavioral pattern in relation to H. pylori infection, with miRNAs acting as fine modulators of the immune response triggered by the pathogen [ 12 , 20 , 31 , 32 ]. Expression alteration seems not to be definitive, with one study proving that eradication of H. pylori infection seems to restore expression of particular miRNA molecules to normal [ 20 ].…”

“…MiRNAs have, however, been proven to play a role in various biologic processes and their dependence upon target gene expression translates into contradictory effects on different organs and tissues [ 11 ]. Given their proven role in the modulation of the innate and adaptative immune response, miRNAs are regarded as key regulators of inflammatory pathways triggered by pathogens such as H. pylori [ 6 , 12 ].…”

“…The presence of the pathogen within the gastric mucosa has been associated with the augmentation of miR-155 expression, a consequence of toll-like receptor (TLR) activation and the release of tumor necrosis factor-alpha (TNF-α) [ 18 ]. Adequate expression of miR-155 is also mandatory to prevent excessive inflammatory responses triggered by H. pylori infection, with miR-155 acting as an integrated part of a negative feedback loop mechanism which will, in the end, inhibit the release of pro-inflammatory cytokines [ 12 , 19 ].…”

Statins’ Regulation of the Virulence Factors of Helicobacter pylori and the Production of ROS May Inhibit the Development of Gastric Cancer

“…In addition to regulating cholesterol synthesis, the virulence factors of H. pylori , and ROS responses, it is possible that statins reduce the risk of H. pylori -associated GC via the regulation of miRNAs and exosomes. For example, miRNA-146 and miRNA-155 are induced after H. pylori infection to regulate inflammation [ 76 , 77 ]. Another miRNA, let-7b is reduced in GC cells in a CagA-dependent manner, which may lead to the downregulation of TLR4 [ 78 ].…”

Innate Immune Responses in Pediatric Patients with Gastritis—A Trademark of Infection or Chronic Inflammation?

“…It is well-documented that this infection might lead to chronic gastritis, peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue lymphomas [ 1 , 2 ]. It was previously demonstrated that H. pylori -associated inflammation is closely related to the host’s innate immune system since it is capable of triggering these responses via particular pathogenicity features such as cag-pathogenicity island (cagPAI) and vacuolating cytotoxin A (VacA), or pathogen-associated molecular patterns (PAMPs), involving flagellin and lipopolysaccharides (LPS) [ 3 , 4 ]. The combination of PAMPs, toll-like receptors (TLRs), and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) results in the activation of immune cells receptors and subsequent promotion of both secretion and expression of several proinflammatory cytokines.…”