{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:19:52Z","timestamp":1792513192130,"version":"4.5.0"},"reference-count":66,"publisher":"National Academy of Sciences","issue":"47","license":[{"start":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T00:00:00Z","timestamp":1620604800000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","award":["CC30430"],"award-info":[{"award-number":["CC30430"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 AI-042347"],"award-info":[{"award-number":["RO1 AI-042347"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004410","name":"European Molecular Biology Organization","doi-asserted-by":"publisher","award":["ALTF 1514-2016"],"award-info":[{"award-number":["ALTF 1514-2016"]}],"id":[{"id":"10.13039\/100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009559","name":"Life Sciences Research Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100009559","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,11,24]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Here, a genome-scale CRISPR\/Cas9 screen in epithelial cells using\n                    <jats:italic>Salmonella<\/jats:italic>\n                    , a prototypical intracellular pathogen, led to the discovery of a new role for IFN-I signaling. We found that this canonical antiviral signaling pathway controls the subcellular localization, protein content, pH, and protease activity of lysosomes. IFN-I signaling-dependent lysosomal acidification was associated with heightened\n                    <jats:italic>Salmonella<\/jats:italic>\n                    virulence gene expression and escape into the cytosol, and\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies confirmed a role for epithelial IFN-I signaling in promoting\n                    <jats:italic>Salmonella<\/jats:italic>\n                    systemic infection. We propose that IFN-I signaling-mediated control of lysosome function contributes to host responses to diverse intracellular pathogens and viruses. Investigating how cytokine signaling modifies organelle function will deepen understanding of the cell biology of innate defense.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2010723117","type":"journal-article","created":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T16:30:21Z","timestamp":1605025821000},"page":"29862-29871","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":36,"title":["Type I interferon remodels lysosome function and modifies intestinal epithelial defense"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4903-010X","authenticated-orcid":false,"given":"Hailong","family":"Zhang","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Insitute, Boston, MA 02115;"},{"name":"Division of Infectious Diseases, Brigham and Women\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Microbiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6973-1755","authenticated-orcid":false,"given":"Abdelrahim","family":"Zoued","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Insitute, Boston, MA 02115;"},{"name":"Division of Infectious Diseases, Brigham and Women\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Microbiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Liu","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Insitute, Boston, MA 02115;"},{"name":"Division of Infectious Diseases, Brigham and Women\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Microbiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2378-3039","authenticated-orcid":false,"given":"Brandon","family":"Sit","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Brigham and Women\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Microbiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1843-7000","authenticated-orcid":false,"given":"Matthew K.","family":"Waldor","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Insitute, Boston, MA 02115;"},{"name":"Division of Infectious Diseases, Brigham and Women\u2019s Hospital, Boston, MA 02115;"},{"name":"Department of Microbiology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,11,10]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-018-0055-5"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2015.01.004"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1821"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-019-0299-y"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.BAI-0022-2019"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E15-03-0144"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-019-0281-8"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00481"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2018.10.003"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1098188"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-018-0011-x"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701386"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2466"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1006098107"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100257"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0882-4010(89)90030-2"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028423"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0323-3"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00652"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.06.010"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2004.00417.x"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02169-19"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2397"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.10.5702-5709.2000"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-micro-092412-155725"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)31620-X"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-6934-0_11"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0171-9335(98)80061-7"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.108.6.2213"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)47429-2"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2000.00955.x"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21814"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-018-0213-2"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1177\/1753425912443392"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12862"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6298"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0809-1"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002116"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.03.008"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.26397-0"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.17.5040-5047.1995"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1098371"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.06.007"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2005.02.002"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10744"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1306376110"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20092720"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3133"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.110.23.2979"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.042678799"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040712"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.05.016"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0065007"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201701107"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500105"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0188600"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007745"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.03.016"},{"key":"e_1_3_4_59_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008498"},{"key":"e_1_3_4_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.07.002"},{"key":"e_1_3_4_61_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038732"},{"key":"e_1_3_4_62_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20192276"},{"key":"e_1_3_4_63_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01345-18"},{"key":"e_1_3_4_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3437"},{"key":"e_1_3_4_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3324"},{"key":"e_1_3_4_66_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-6581-6_19"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.2010723117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2010723117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T07:13:08Z","timestamp":1649833988000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.2010723117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,10]]},"references-count":66,"journal-issue":{"issue":"47","published-print":{"date-parts":[[2020,11,24]]}},"alternative-id":["10.1073\/pnas.2010723117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2010723117","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,10]]},"assertion":[{"value":"2020-11-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}