Abstract
Helicobacter pylori-induced chronic gastritis represents a well-established risk factor for gastric cancer (GC). However, the mechanism by which chronic inflammation caused by H. pylori induces the development of GC is unclear. H. pylori can influence host cell signalling pathways to induce gastric disease development and mediate cancer promotion and progression. Toll-like receptors (TLRs), as pattern recognition receptors (PRRs), play a key role in the gastrointestinal innate immune response, and their signalling has been implicated in the pathogenesis of an increasing number of inflammation-associated cancers. The core adapter myeloid differentiation factor-88 (MyD88) is shared by most TLRs and functions primarily in H. pylori-triggered innate immune signalling. MyD88 is envisioned as a potential target for the regulation of immune responses and is involved in the regulation of tumourigenesis in a variety of cancer models. In recent years, the TLR/MyD88 signalling pathway has received increasing attention for its role in regulating innate and adaptive immune responses, inducing inflammatory activation and promoting tumour formation. In addition, TLR/MyD88 signalling can manipulate the expression of infiltrating immune cells and various cytokines in the tumour microenvironment (TME). In this review, we discuss the pathogenetic regulatory mechanisms of the TLR/MyD88 signalling cascade pathway and its downstream molecules in H. pylori infection-induced-associated GC. The focus is to elucidate the immunomolecular mechanisms of pathogen recognition and innate immune system activation of H. pylori in the TME of inflammation-associated GC. Ultimately, this study will provide insight into the mechanism of H. pylori-induced chronic inflammation-induced GC development and provide thoughts for GC prevention and treatment strategies.
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Abbreviations
- APC:
-
Antigen-presenting cell
- ATRA:
-
all-trans retinoic acid
- BMDC:
-
Bone marrow‐derived cell
- BMDM:
-
Bone marrow‐derived macrophage
- Cag:
-
Cytotoxin-related gene
- CCRL:
-
C-C motif chemokine receptor-like
- cDC:
-
Conventional DC
- COX:
-
Cyclooxygenase
- CTL:
-
Cytotoxic T lymphocyte
- CXCL:
-
Chemokine (CXC motif) ligand
- DAMP:
-
Damage-associated molecular pattern
- DC:
-
Dendritic cell
- NKG2D:
-
Natural killer group2 member
- NKG2DL:
-
Natural killer group2 member ligand
- GC:
-
Gastric cancer
- GM-CSF::
-
Granulocyte macrophage–colony-stimulating factor
- HKHP:
-
Thermal killing of Helicobacter pylori
- HMGB:
-
High-mobility group box
- Hop:
-
Toxicity-associated adhesin
- HP-NAP:
-
Helicobacter pylori Neutrophil-activating protein
- H. pylori:
-
Helicobacter pylori
- IFN:
-
Interferon
- IL:
-
Interleukin
- IRF:
-
IFN regulatory factor
- JAK:
-
Janus kinase
- LPS:
-
Lipopolysaccharide
- MAP:
-
Mitogen-activated protein
- miRNA:
-
MicroRNA
- MNC:
-
Monocyte
- MyD88:
-
Myeloid differentiation factor-88
- Mø:
-
Macrophage
- NEUT:
-
Neutrophil
- NF‐κB:
-
Nuclear factor‐κB;
- NK cell:
-
Natural killer cell
- NLR:
-
Nod-like receptors
- PAMP:
-
Pathogen-associated molecular pattern
- PAR:
-
Protease-activated receptor
- pDC:
-
Plasmacytoid dendritic cell
- PD-L1:
-
Programmed death ligand-1
- PGE2:
-
Prostaglandin E2
- ROS:
-
Reactive oxygen species
- PRR:
-
Pattern recognition receptor
- SLFN4:
-
The myeloid differentiation factor Schlafen4
- STAT:
-
Signal transducer and transcription factor
- TAK:
-
TNF-α receptor-associated factor-related kinase
- TAM:
-
Tumour-associated macrophage
- TCGA:
-
The Cancer Genome Atlas
- Th:
-
T helper cell
- TIL:
-
Tumour infiltrating lymphocyte
- Tim-3:
-
T cell immunoglobulin and mucin-domain-containing molecule-3
- TIR:
-
Toll/IL-1 receptor
- TLR:
-
Toll-like receptor
- TME:
-
The tumour microenvironment
- TNF‐α:
-
Tumour necrosis factor‐α
- TRAF:
-
TNF-α receptor-associated factor
- Tr-1:
-
Tregulatory-1
- T4ss:
-
Type IV secretion system
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Funding
This work was supported by the Youth Program of National Natural Science Foundation of China (No. 81500169), the Hunan Province Key Laboratory of Tumour Cellular & Molecular Pathology (2016TP1015) and the Key Project of Hunan Provincial Health Commission (20201921).
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Meiqi Liu is responsible for writing the article. Zhizhong Hu is responsible for figure modification and article format adjustment. Yang Zhang and Chengkun Wang are responsible for the direction and core of the article. All authors have read and approved the publication of this article.
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Liu, M., Hu, Z., Wang, C. et al. The TLR/MyD88 signalling cascade in inflammation and gastric cancer: the immune regulatory network of Helicobacter pylori. J Mol Med 101, 767–781 (2023). https://doi.org/10.1007/s00109-023-02332-5
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DOI: https://doi.org/10.1007/s00109-023-02332-5