TRIF-IFN-I pathway in Helicobacter-induced gastric cancer in an accelerated murine disease model and patient biopsies

• Published in: iScience 2024-04, Vol.27 (4), p.109457, Article 109457
• Main Authors: Bali, Prerna, Lozano-Pope, Ivonne, Hernandez, Jonathan, Estrada, Monica V., Corr, Maripat, Turner, Michael A., Bouvet, Michael, Benner, Christopher, Obonyo, Marygorret
• Format: Article
• Language: English
• Subjects: Biological sciences; Cancer; Clinical microbiology; Microbiology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.109457

Helicobacter pylori (H. pylori) infection is a known cause of many digestive diseases, including gastritis, peptic ulcers, and gastric cancer. However, the underlying mechanisms by which H. pylori infection triggers these disorders are still not clearly understood. Gastric cancer is a slow progressing disease, which makes it difficult to study. We have developed an accelerated disease progression mouse model, which leverages mice deficient in the myeloid differentiation primary response 88 gene (Myd88−/−) infected with Helicobacter felis (H. felis). Using this model and gastric biopsy samples from patients, we report that activation of the Toll/interleukin-1 receptor (TIR)-domain-containing adaptor inducing interferon-β (TRIF)-type I interferon (IFN-I) signaling pathway promotes Helicobacter-induced disease progression toward severe gastric pathology and gastric cancer development. Further, results implicated downstream targets of this pathway in disease pathogenesis. These findings may facilitate stratification of Helicobacter-infected patients and thus enable treatment prioritization of patients. [Display omitted] •Helicobacter-induced gastric cancer (GC) progresses rapidly in absence of MyD88•Absence of TRIF decreased Helicobacter induced disease pathology•ISGs upregulated in Helicobacter infected Myd88−/− mice and GC patients•TRIF-IFN-I pathway plays pivotal role in development of Helicobacter-induced GC Biological sciences; Microbiology; Clinical microbiology; Cancer