{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:28:00Z","timestamp":1785414480160,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,27]]},"group-title":"Immunology","reference-count":90,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI143796"],"award-info":[{"award-number":["AI143796"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00yt0ea73","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005886","name":"Pediatric Infectious Diseases Society","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005886","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,27]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Macrophages maintain tissue homeostasis by phagocytosing spent cells, recycling nutrients, and mounting antimicrobial responses to eliminate pathogens. Yet, they can also act as a cellular niche and organize granulomas that enable intracellular bacteria, such as\n                  <jats:italic>Salmonella enterica<\/jats:italic>\n                  , to persist in infected tissues. Here, using a murine\n                  <jats:italic>Salmonella<\/jats:italic>\n                  Typhimurium (\n                  <jats:italic>S<\/jats:italic>\n                  Tm) infection model, we find that granuloma formation and bacterial persistence are dependent on SPIC, which controls development of VCAM1\n                  <jats:sup>+<\/jats:sup>\n                  macrophages critical for erythrocyte, heme, and iron recycling. VCAM1\n                  <jats:sup>+<\/jats:sup>\n                  macrophages markedly increase in infected spleens and have high levels of erythrophagocytosis, intracellular bacteria, and T-cell co-stimulatory ligands. Using SPIC-deficient mice generated from CRISPR gene editing, we show that SPIC is required for macrophage co-stimulatory ligand expression and formation of a VCAM1\n                  <jats:sup>+<\/jats:sup>\n                  macrophage zone that produces CXCL9 retaining T cells at the granuloma periphery. SPIC deletion abolishes this granuloma cellular architecture and reduces bacterial persistence. We propose that SPIC-dependent erythrophagocytic macrophages drive granuloma formation and bacterial tissue persistence.\n                <\/jats:p>","DOI":"10.64898\/2026.05.24.727563","type":"posted-content","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T06:30:12Z","timestamp":1779949812000},"source":"Crossref","is-referenced-by-count":0,"title":["SPIC-dependent erythrophagocytic macrophages drive granuloma formation and pathogen persistence during intracellular bacterial infection"],"prefix":"10.64898","author":[{"given":"Aaron","family":"Fountain","sequence":"first","affiliation":[{"name":"Departments of Pediatrics, Stanford University School of Medicine, Stanford, CA"},{"name":"Departments of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixian","family":"Lin","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Stanford University School of Medicine, Stanford, CA"},{"name":"Departments of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max J.","family":"Lain","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Stanford University School of Medicine, Stanford, CA"},{"name":"Departments of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Xue","sequence":"additional","affiliation":[{"name":"ClearNote Health, San Mateo, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2724-2547","authenticated-orcid":false,"given":"Trung H. 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