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We apply single-cell transcriptomics to investigate macrophage functional diversity during persistent\n                    <jats:italic>S. enterica<\/jats:italic>\n                    serovar Typhimurium (\n                    <jats:italic>S<\/jats:italic>\n                    Tm) infection in mice. We identify determinants of macrophage heterogeneity in infected spleens and describe populations of distinct phenotypes, functional programming, and spatial localization. Using an\n                    <jats:italic>S<\/jats:italic>\n                    Tm mutant with impaired ability to polarize macrophage phenotypes, we find that angiotensin-converting enzyme (ACE) defines a granuloma macrophage population that is nonpermissive for intracellular bacteria, and their abundance anticorrelates with tissue bacterial burden. Disruption of pathogen control by neutralizing TNF is linked to preferential depletion of ACE\n                    <jats:sup>+<\/jats:sup>\n                    macrophages in infected tissues. Thus, ACE\n                    <jats:sup>+<\/jats:sup>\n                    macrophages have limited capacity to serve as cellular niche for intracellular bacteria to establish persistent infection.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.add4333","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T16:36:19Z","timestamp":1674232579000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":29,"title":["Single-cell profiling identifies ACE\n                    <sup>+<\/sup>\n                    granuloma macrophages as a nonpermissive niche for intracellular bacteria during persistent\n                    <i>Salmonella<\/i>\n                    infection"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2724-2547","authenticated-orcid":true,"given":"Trung H.\u00a0M.","family":"Pham","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University, School of Medicine, Stanford, CA, USA."},{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7846-4273","authenticated-orcid":true,"given":"Yuan","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2556-8829","authenticated-orcid":true,"given":"Susan M.","family":"Brewer","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University, School of Medicine, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5435-8663","authenticated-orcid":true,"given":"Kenneth E.","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1613-0809","authenticated-orcid":true,"given":"Stephen R.","family":"Quake","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Stanford University, Stanford, CA, USA."},{"name":"Chan Zuckerberg Biohub, San\u00a0Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3804-2209","authenticated-orcid":true,"given":"Denise M.","family":"Monack","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Stanford University, School of Medicine, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001921"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.76"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031319"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00592-09"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12266"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01028"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-100022"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.VMBF-0020-2015"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.10.009"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2019.11.011"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.04.004"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2017.42"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.3.6.611"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.20.3.267"},{"key":"e_1_3_3_16_2","first-page":"63","article-title":"Enteric fever: A clinicopathologic study of 104 cases","volume":"69","author":"Nasrallah S. 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