{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:11:12Z","timestamp":1788502272095,"version":"build-2803163510"},"reference-count":72,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"3","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,1,17]]},"abstract":"<jats:p>\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    (MTB) ESX-1, a type VII secretion system, is a key virulence determinant contributing to MTB\u2019s survival within lung mononuclear phagocytes (MNPs), but its effect on MNP recruitment and differentiation remains unknown. Here, using multiple single-cell RNA sequencing techniques, we studied the role of ESX-1 in MNP heterogeneity and response in mice and murine bone marrow\u2013derived macrophages (BMDM). We found that ESX-1 is required for MTB to recruit diverse MNP subsets with high MTB burden. Further, MTB induces a transcriptional signature of immune evasion in lung macrophages and BMDM in an ESX-1\u2013dependent manner. Spatial transcriptomics revealed an up-regulation of permissive features within MTB lesions, where monocyte-derived macrophages concentrate near MTB-infected cells. Together, our findings suggest that MTB ESX-1 facilitates the recruitment and differentiation of MNPs, which MTB can infect and manipulate for survival. Our dataset across various models and methods could contribute to the broader understanding of recruited cell heterogeneity during MTB lung infection.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adq8158","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T14:00:44Z","timestamp":1736949644000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":23,"title":["Single-cell analysis reveals\n                    <i>Mycobacterium tuberculosis<\/i>\n                    ESX-1\u2013mediated accumulation of permissive macrophages in infected mouse lungs"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8038-1207","authenticated-orcid":true,"given":"Weihao","family":"Zheng","sequence":"first","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4527-3370","authenticated-orcid":true,"given":"Michael","family":"Borja","sequence":"additional","affiliation":[{"name":"Chan Zuckerberg Biohub, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5511-887X","authenticated-orcid":true,"given":"Leah C.","family":"Dorman","sequence":"additional","affiliation":[{"name":"Chan Zuckerberg Biohub, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0204-0105","authenticated-orcid":true,"given":"Jonathan","family":"Liu","sequence":"additional","affiliation":[{"name":"Chan Zuckerberg Biohub, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3383-0855","authenticated-orcid":true,"given":"Andy","family":"Zhou","sequence":"additional","affiliation":[{"name":"Chan Zuckerberg Biohub, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9031-115X","authenticated-orcid":true,"given":"Amanda","family":"Seng","sequence":"additional","affiliation":[{"name":"Chan Zuckerberg Biohub, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1416-5154","authenticated-orcid":true,"given":"Ritwicq","family":"Arjyal","sequence":"additional","affiliation":[{"name":"Chan Zuckerberg Biohub, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-5063","authenticated-orcid":true,"given":"Sara","family":"Sunshine","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0348-417X","authenticated-orcid":true,"given":"Alina","family":"Nalyvayko","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0142-2355","authenticated-orcid":true,"given":"Angela Oliveira","family":"Pisco","sequence":"additional","affiliation":[{"name":"Chan Zuckerberg Biohub, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5736-4388","authenticated-orcid":true,"given":"Oren S.","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of California, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7141-5420","authenticated-orcid":true,"given":"Norma","family":"Neff","sequence":"additional","affiliation":[{"name":"Chan Zuckerberg Biohub, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4190-2823","authenticated-orcid":true,"given":"Beth Shoshana","family":"Zha","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Medicine, University of California, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"World Health Organization Global Tuberculosis Report 2022 (Geneva 2022)."},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aaw6693"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.08.001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011871"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.4.2016"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01332-22"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.22028"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007154"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.4.2509"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.9.6349"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008621"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1012205"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.8.4501-4509.2002"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.3.271"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12217"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071367"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1620133114"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00614-08"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1179663"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tube.2014.01.004"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.03237.x"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2235593100"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.1.546-551.2005"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2639"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0276-y"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.52983"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth996"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.4.2170-2176.2004"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2015.1102832"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.4589"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.08.007"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41695-z"},{"key":"e_1_3_2_34_2","doi-asserted-by":"crossref","unstructured":"K. Li Z. Ouyang D. Lin M. Mingueneau W. Chen D. Sexton B. Zhang cellxgene VIP unleashes full power of interactive visualization plotting and analysis of scRNA-seq data in the scale of millions of cells 2 3. bioRxiv 590421 [Preprint] (2020).","DOI":"10.1101\/2020.08.28.270652"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0844-5"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abl7482"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13489"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500434"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2011.7"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.12.002"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.03.066"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601370"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aax6337"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200535496"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00542"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0433-8"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102571"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2018.05.011"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0909610"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.3923\/jas.2008.719.722"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22620-3"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.04.043"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02427"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002781"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa6090"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.202201701"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-015-0538-9"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2496-1"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau0964"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2321"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108337"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20210615"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.12.6166"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.126556"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1362-4"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11624"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41385-020-00342-x"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040433"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.150060"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09816-4"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.876321"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2020.02.005"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0153079"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adq8158","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T14:00:52Z","timestamp":1736949652000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adq8158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,17]]},"references-count":72,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,1,17]]}},"alternative-id":["10.1126\/sciadv.adq8158"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adq8158","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.04.20.590421","asserted-by":"object"}]},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,17]]},"assertion":[{"value":"2024-06-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadq8158"}}