{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:02:45Z","timestamp":1785196965132,"version":"3.55.0"},"reference-count":74,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The global rise of antibiotic-resistant strains of<jats:italic>Salmonella<\/jats:italic>has necessitated the development of alternative therapeutic strategies. Recent studies have shown that targeting host factors may provide an alternative approach for the treatment of intracellular pathogens. Host-directed therapy (HDT) modulates host cellular factors that are essential to support the replication of the intracellular pathogens. In the current study, we identified Gefitinib as a potential host directed therapeutic drug against<jats:italic>Salmonella<\/jats:italic>. Further, using the proteome analysis of<jats:italic>Salmonella<\/jats:italic>-infected macrophages, we identified EGFR, a host factor, promoting intracellular survival of<jats:italic>Salmonella via<\/jats:italic>mTOR-HIF-1\u03b1 axis. Blocking of EGFR, mTOR or HIF-1\u03b1 inhibits the intracellular survival of<jats:italic>Salmonella<\/jats:italic>within the macrophages and in mice. Global proteo-metabolomics profiling indicated the upregulation of host factors predominantly associated with ATP turn over, glycolysis, urea cycle, which ultimately promote the activation of EGFR-HIF1\u03b1 signaling upon infection. Importantly, inhibition of EGFR and HIF1\u03b1 restored both proteomics and metabolomics changes caused by<jats:italic>Salmonella<\/jats:italic>infection. Taken together, this study identifies Gefitinib as a host directed drug that holds potential translational values against<jats:italic>Salmonella<\/jats:italic>infection and might be useful for the treatment of other intracellular infections.<\/jats:p>","DOI":"10.3389\/fimmu.2021.648710","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T06:18:20Z","timestamp":1617171500000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Gefitinib Results in Robust Host-Directed Immunity Against Salmonella Infection Through Proteo-Metabolomic Reprogramming"],"prefix":"10.3389","volume":"12","author":[{"given":"Srikanth","family":"Sadhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaigham Abbas","family":"Rizvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramendra 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