Author:
Bali Prerna,Lozano-Pope Ivonne,Hernandez Jonathan,Estrada Monica V,Corr Maripat,Turner Michael A.,Bouvet Michael,Benner Christopher,Obonyo Marygorret
Abstract
AbstractHelicobacter pylori(H. pylori)infection is an established cause of many digestive diseases, including gastritis, peptic ulcers, and gastric cancer. However, the mechanism by which infection withH. pyloricauses these disorders is still not clearly understood. This is due to insufficient knowledge of pathways that promoteH. pylori-induced disease progression. We have established aHelicobacter-induced accelerated disease progression mouse model, which involves infecting mice deficient in the myeloid differentiation primary response 88 gene (Myd88-/-) withH. felis. Using this model, we report here that that progression ofH. felis-induced inflammation to high-grade dysplasia was associated with activation of type I interferon (IFN-I) signaling pathway and upregulation of related downstream target genes, IFN-stimulated genes (ISGs). These observations were further corroborated by the enrichment of ISRE motifs in the promoters of upregulated genes. Further we showed thatH. felis-induced inflammation in mice deficient in Toll/interleukin-1 receptor (TIR)-domain-containing adaptor inducing interferon-β (TRIF,TrifLps2) did not progress to severe gastric pathology, indicating a role of the TRIF signaling pathway in disease pathogenesis and progression. Indeed, survival analysis in gastric biopsy samples from gastric cancer patients illustrated that high expression ofTrifwas significantly associated with poor survival in gastric cancer.
Publisher
Cold Spring Harbor Laboratory
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