{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:51:45Z","timestamp":1792601505234,"version":"4.5.0"},"reference-count":67,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"782","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Signal."],"published-print":{"date-parts":[[2023,4,25]]},"abstract":"<jats:p>Macrophages are key cellular contributors to the pathogenesis of COVID-19, the disease caused by the virus SARS-CoV-2. The SARS-CoV-2 entry receptor ACE2 is present only on a subset of macrophages at sites of SARS-CoV-2 infection in humans. Here, we investigated whether SARS-CoV-2 can enter macrophages, replicate, and release new viral progeny; whether macrophages need to sense a replicating virus to drive cytokine release; and, if so, whether ACE2 is involved in these mechanisms. We found that SARS-CoV-2 could enter, but did not replicate within, ACE2-deficient human primary macrophages and did not induce proinflammatory cytokine expression. By contrast, ACE2 overexpression in human THP-1\u2013derived macrophages permitted SARS-CoV-2 entry, processing and replication, and virion release. ACE2-overexpressing THP-1 macrophages sensed active viral replication and triggered proinflammatory, antiviral programs mediated by the kinase TBK-1 that limited prolonged viral replication and release. These findings help elucidate the role of ACE2 and its absence in macrophage responses to SARS-CoV-2 infection.<\/jats:p>","DOI":"10.1126\/scisignal.abq1366","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T17:58:57Z","timestamp":1682445537000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":46,"title":["Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9098-4493","authenticated-orcid":true,"given":"Larisa I.","family":"Labzin","sequence":"first","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."},{"name":"IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia."},{"name":"Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keng Yih","family":"Chew","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Eschke","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."},{"name":"IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8459-1853","authenticated-orcid":true,"given":"Tyron","family":"Esposito","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."},{"name":"IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6120-2851","authenticated-orcid":true,"given":"Claudia J.","family":"Stocks","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."},{"name":"IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0525-2154","authenticated-orcid":true,"given":"James","family":"Rae","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."},{"name":"Centre for Microscopy and Microanalysis, University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0956-1026","authenticated-orcid":true,"given":"Ralph","family":"Patrick","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6051-3268","authenticated-orcid":true,"given":"Helen","family":"Mostafavi","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Hill","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4801-0673","authenticated-orcid":true,"given":"Teodor E.","family":"Yordanov","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2231-0136","authenticated-orcid":true,"given":"Caroline L.","family":"Holley","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."},{"name":"IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3851-335X","authenticated-orcid":true,"given":"Stefan","family":"Emming","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."},{"name":"IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3407-1758","authenticated-orcid":true,"given":"Svenja","family":"Fritzlar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3754-2642","authenticated-orcid":true,"given":"Francesca L.","family":"Mordant","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Steinfort","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Melbourne, Parkville, VIC 3010, Australia."},{"name":"Department of Respiratory Medicine, Royal Melbourne Hospital, Parkville, VIC 3052, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1713-3056","authenticated-orcid":true,"given":"Kanta","family":"Subbarao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia."},{"name":"WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4631-5633","authenticated-orcid":true,"given":"Christian M.","family":"Nefzger","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne K.","family":"Lagendijk","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4723-4173","authenticated-orcid":true,"given":"Emma J.","family":"Gordon","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7494-5248","authenticated-orcid":true,"given":"Robert G.","family":"Parton","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."},{"name":"Centre for Microscopy and Microanalysis, University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4963-6184","authenticated-orcid":true,"given":"Kirsty R.","family":"Short","sequence":"additional","affiliation":[{"name":"Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia."},{"name":"School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0989-4971","authenticated-orcid":true,"given":"Sarah L.","family":"Londrigan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9261-3805","authenticated-orcid":true,"given":"Kate","family":"Schroder","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience (IMB), University of Queensland, Brisbane, QLD 4072, Australia."},{"name":"IMB Centre for Inflammation and Disease Research, University of Queensland, Brisbane, QLD 4072, Australia."},{"name":"Australian Infectious Diseases Research Centre, University of Queensland, Brisbane, QLD 4072, Australia."},{"name":"School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, QLD 4072, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.02.052"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-021-00418-x"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-020-00468-6"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04474-x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.042"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.026"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021107826"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.006"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0602-4"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.720109"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0331-4"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa753"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa356"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.045021-0"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.156.2.621"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2019.11.003"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140825"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.07.013"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004053"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03570-8"},{"key":"e_1_3_3_22_2","doi-asserted-by":"crossref","unstructured":"T. T.-H. Wu K.\u00a0J.\u00a0Travaglini A.\u00a0Rustagi D.\u00a0Xu Y.\u00a0Zhang S.\u00a0K.\u00a0Jang A.\u00a0Gillich R.\u00a0Dehghannasiri G.\u00a0Martinez-Colon A.\u00a0Beck A.\u00a0J.\u00a0Wilk M.\u00a0Morri W.\u00a0L.\u00a0Trope J.\u00a0B.\u00a0Shrager S.\u00a0R.\u00a0Quake C.\u00a0S.\u00a0Kuo J.\u00a0Salzman P.\u00a0S.\u00a0Kim C.\u00a0A.\u00a0Blish M.\u00a0A.\u00a0Krasnow Activated interstitial macrophages are a predominant target of viral takeover and focus of inflammation in COVID-19 initiation in human lung. bioRxiv 2022.05.10.491266 [ Preprint ]. 2022. https:\/\/doi.org\/10.1101\/2022.05.10.491266.","DOI":"10.1101\/2022.05.10.491266"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04802-1"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.741502"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202051252"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.647824"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.05.006"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03569-1"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1906-x"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-01227-z"},{"key":"e_1_3_3_31_2","doi-asserted-by":"crossref","unstructured":"M. Magnen R.\u00a0You A.\u00a0A.\u00a0Rao R.\u00a0T.\u00a0Davis L.\u00a0Rodriguez C.\u00a0R.\u00a0Simoneau L.\u00a0Hysenaj K.\u00a0H.\u00a0Hu T.\u00a0U.\u00a0C. Consortium C.\u00a0Love P.\u00a0G.\u00a0Woodruff D.\u00a0J.\u00a0Erle C.\u00a0M.\u00a0Hendrickson C.\u00a0S.\u00a0Calfee M.\u00a0A.\u00a0Matthay J.\u00a0P.\u00a0Roose A.\u00a0Sil M.\u00a0Ott C.\u00a0R.\u00a0Langelier M.\u00a0F.\u00a0Krummel M.\u00a0R.\u00a0Looney Immediate myeloid depot for SARS-CoV-2 in the human lung. bioRxiv 2022.04.28.489942 [ Preprint ]. 2022. https:\/\/doi.org\/10.1101\/2022.04.28.489942.","DOI":"10.21203\/rs.3.rs-1639631\/v1"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.05.014"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/cti2.1350"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010479"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018101365"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1093616"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.01.012"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2588-y"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100208"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.05.010"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-20542-0"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04702-4"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2014.03.006"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.000414"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-020-04138-6"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.28643"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1139\/gen-2020-0124"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd4570"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abl4340"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03148-w"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74443"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00937-x"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02415-20"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-92940-3"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc3545"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc2061"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3665"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202100872"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.644574"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-019-0277-7"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI98224"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1097\/LBR.0000000000000201"},{"key":"e_1_3_3_64_2","doi-asserted-by":"crossref","unstructured":"J.\u00a0Q.\u00a0Davies S.\u00a0Gordon Isolation and culture of human macrophages in Basic Cell Culture Protocols C.\u00a0D.\u00a0Helgason C.\u00a0L.\u00a0Miller Eds. (Humana Press 2005) pp.\u00a0105\u2013116.","DOI":"10.1385\/1-59259-838-2:105"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.08.045"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.11.8463-8471.1998"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201002119"}],"container-title":["Science Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scisignal.abq1366","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T12:39:11Z","timestamp":1705408751000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scisignal.abq1366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,25]]},"references-count":67,"journal-issue":{"issue":"782","published-print":{"date-parts":[[2023,4,25]]}},"alternative-id":["10.1126\/scisignal.abq1366"],"URL":"https:\/\/doi.org\/10.1126\/scisignal.abq1366","relation":{},"ISSN":["1945-0877","1937-9145"],"issn-type":[{"value":"1945-0877","type":"print"},{"value":"1937-9145","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,25]]},"assertion":[{"value":"2022-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eabq1366"}}