{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:47:52Z","timestamp":1768506472472,"version":"3.49.0"},"posted":{"date-parts":[[2023,6,6]]},"group-title":"Cancer Biology","reference-count":51,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,8,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Helicobacter pylori<\/jats:italic>\n                  (\n                  <jats:italic>H. pylori)<\/jats:italic>\n                  infection is an established cause of many digestive diseases, including gastritis, peptic ulcers, and gastric cancer. However, the mechanism by which infection with\n                  <jats:italic>H. pylori<\/jats:italic>\n                  causes these disorders is still not clearly understood. This is due to insufficient knowledge of pathways that promote\n                  <jats:italic>H. pylori<\/jats:italic>\n                  -induced disease progression. We have established a\n                  <jats:italic>Helicobacter<\/jats:italic>\n                  -induced accelerated disease progression mouse model, which involves infecting mice deficient in the myeloid differentiation primary response 88 gene (\n                  <jats:italic>\n                    Myd88\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  ) with\n                  <jats:italic>H. felis<\/jats:italic>\n                  . Using this model, we report here that that progression of\n                  <jats:italic>H. felis<\/jats:italic>\n                  -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 that\n                  <jats:italic>H. felis<\/jats:italic>\n                  -induced inflammation in mice deficient in Toll\/interleukin-1 receptor (TIR)-domain-containing adaptor inducing interferon-\u03b2 (TRIF,\n                  <jats:italic>\n                    Trif\n                    <jats:sup>Lps<\/jats:sup>\n                  <\/jats:italic>\n                  <jats:sup>2<\/jats:sup>\n                  ) 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 of\n                  <jats:italic>Trif<\/jats:italic>\n                  was significantly associated with poor survival in gastric cancer.\n                <\/jats:p>","DOI":"10.1101\/2023.06.04.543598","type":"posted-content","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T20:02:15Z","timestamp":1686081735000},"source":"Crossref","is-referenced-by-count":0,"title":["Activation of the TRIF pathway and downstream targets results in the development of precancerous lesions during infection with\n                  <i>Helicobacter<\/i>"],"prefix":"10.64898","author":[{"given":"Prerna","family":"Bali","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivonne","family":"Lozano-Pope","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Hernandez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica V","family":"Estrada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maripat","family":"Corr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Bouvet","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Benner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marygorret","family":"Obonyo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023082102150704000_2023.06.04.543598v3.1","first-page":"1","article-title":"Schistomes, liver flukes and Helicobacter pylori. 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