{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T15:43:57Z","timestamp":1776354237677,"version":"3.51.2"},"reference-count":29,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2018,3,1]],"date-time":"2018-03-01T00:00:00Z","timestamp":1519862400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["DK084246"],"award-info":[{"award-number":["DK084246"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AI53459"],"award-info":[{"award-number":["AI53459"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The host employs both cell-autonomous and system-level responses to limit pathogen replication in the initial stages of infection. Previously, we reported that the eukaryotic initiation factor 2\u03b1 (eIF2\u03b1) kinases heme-regulated inhibitor (HRI) and protein kinase R (PKR) control distinct cellular and immune-related activities in response to diverse bacterial pathogens. Specifically for\n                    <jats:named-content content-type=\"genus-species\">Listeria monocytogenes<\/jats:named-content>\n                    , there was reduced translocation of the pathogen to the cytosolic compartment in HRI-deficient cells and consequently reduced loading of pathogen-derived antigens on major histocompatibility complex class I (MHC-I) complexes. Here we show that\n                    <jats:italic>Hri<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, as well as wild-type mice treated with an HRI inhibitor, are more susceptible to listeriosis. In the first few hours of\n                    <jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content>\n                    infection, there was much greater pathogen proliferation in the liver of\n                    <jats:italic>Hri<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice than in the liver of\n                    <jats:italic>Hri<\/jats:italic>\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice. Further, there was a rapid increase of serum interleukin-6 (IL-6) levels in\n                    <jats:italic>Hri<\/jats:italic>\n                    <jats:sup>+\/+<\/jats:sup>\n                    mice in the first few hours of infection whereas the increase in IL-6 levels in\n                    <jats:italic>Hri<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice was notably delayed. Consistent with these\n                    <jats:italic>in vivo<\/jats:italic>\n                    findings, the rate of listeriolysin O (LLO)-dependent pathogen efflux from infected\n                    <jats:italic>Hri<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    macrophages and fibroblasts was significantly higher than the rate seen with infected\n                    <jats:italic>Hri<\/jats:italic>\n                    <jats:sup>+\/+<\/jats:sup>\n                    cells. Treatment of cells with an eIF2\u03b1 kinase activator enhanced both the HRI-dependent and PKR-dependent infection phenotypes, further indicating the pharmacologically malleability of this signaling pathway. Collectively, these results suggest that HRI mediates the cellular confinement and killing of virulent\n                    <jats:named-content content-type=\"genus-species\">L. monocytogenes<\/jats:named-content>\n                    in addition to promoting a system-level cytokine response and that both are required to limit pathogen replication during the first few hours of infection.\n                  <\/jats:p>","DOI":"10.1128\/iai.00707-17","type":"journal-article","created":{"date-parts":[[2018,1,8]],"date-time":"2018-01-08T07:01:08Z","timestamp":1515394868000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["The eIF2\u03b1 Kinase Heme-Regulated Inhibitor Protects the Host from Infection by Regulating Intracellular Pathogen Trafficking"],"prefix":"10.1128","volume":"86","author":[{"given":"Wael","family":"Bahnan","sequence":"first","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin C.","family":"Boucher","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Petoria","family":"Gayle","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niraj","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Rosen","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, San Diego, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bertal","family":"Aktas","sequence":"additional","affiliation":[{"name":"Hematology Laboratory for Translational Research, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Becky","family":"Adkins","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arba","family":"Ager","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wasif N.","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Miami Miller School of Medicine, Miami, Florida, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0515-3850","authenticated-orcid":false,"given":"Kurt","family":"Schesser","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology, University of Miami Miller School of Medicine, Miami, Florida, 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