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

Prerna Bali; Ivonne Lozano-Pope; Jonathan Hernandez; Monica V. Estrada; Maripat Corr; Michael A. Turner; Michael Bouvet; Christopher Benner; Marygorret Obonyo

iScience (Apr 2024)

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

Prerna Bali,
Ivonne Lozano-Pope,
Jonathan Hernandez,
Monica V. Estrada,
Maripat Corr,
Michael A. Turner,
Michael Bouvet,
Christopher Benner,
Marygorret Obonyo

Affiliations

Prerna Bali: Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA
Ivonne Lozano-Pope: Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA
Jonathan Hernandez: Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA
Monica V. Estrada: Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA
Maripat Corr: Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA
Michael A. Turner: Department of Surgery, University of California, San Diego, La Jolla, CA, USA; VA San Diego Healthcare System, San Diego, CA, USA
Michael Bouvet: Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA; Department of Surgery, University of California, San Diego, La Jolla, CA, USA; VA San Diego Healthcare System, San Diego, CA, USA
Christopher Benner: Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA
Marygorret Obonyo: Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA; Moores Cancer Center, University of California, San Diego, La Jolla, CA, USA; Corresponding author

Journal volume & issue: Vol. 27, no. 4
p. 109457

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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