{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:38:43Z","timestamp":1785418723858,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,1]]},"group-title":"Immunology","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["T32 HL007185"],"award-info":[{"award-number":["T32 HL007185"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F32 HL162424"],"award-info":[{"award-number":["F32 HL162424"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30 AI168440"],"award-info":[{"award-number":["P30 AI168440"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R25 AI147375"],"award-info":[{"award-number":["R25 AI147375"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R35 HL161241"],"award-info":[{"award-number":["R35 HL161241"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 AI051242"],"award-info":[{"award-number":["R01 AI051242"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CA-1253559"],"award-info":[{"award-number":["CA-1253559"]}],"id":[{"id":"https:\/\/ror.org\/01p3rh655","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Infection by\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  (Mtb) is characterized by pathogen persistence in lung cells derived from blood monocytes. Since monocyte-derived lung subsets differ in their ability to restrict the growth of intracellular Mtb in mice, understanding the ontogeny of these subsets can inform development of host-directed therapies. Circulating monocytes are proposed to be heterogeneous, arising from distinct bone marrow or spleen progenitors that direct local differentiation. However, the role of the Mtb-infected lung environment in this process has not been addressed. We found that infected and uninfected mice had similar bone marrow monopoiesis, resulting in equivalent monocyte differentiation within the infected lung. While pulmonary Mtb infection also induced splenic monopoiesis, we found no impact on lung monocyte differentiation in splenectomized mice. However, when wildtype monocytes were transferred into Mtb-infected\n                  <jats:italic>\n                    Sp140\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  recipients, in which excess Type I interferons and neutrophils alter the lung environment, we observed that donor-derived lung subsets resembled recipient-derived cells. In the lungs of Mtb-infected mice, we identified monocyte-derived lung subsets with unique gene expression, associated with specific spatial distributions and cell neighborhoods. These findings suggest that the local lung environment has a larger influence on the phenotypic diversity of monocyte-derived lung cells than does the peripheral environment.\n                <\/jats:p>","DOI":"10.64898\/2026.06.25.734601","type":"posted-content","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:20:13Z","timestamp":1782919213000},"source":"Crossref","is-referenced-by-count":0,"title":["The lung tissue environment in\n                  <i>Mycobacterium tuberculosis<\/i>\n                  infection determines local monocyte differentiation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0400-6146","authenticated-orcid":false,"given":"Alexander","family":"Mohapatra","sequence":"first","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8038-1207","authenticated-orcid":false,"given":"Weihao","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longhui","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Laboratory Medicine, University of California, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Looney","sequence":"additional","affiliation":[{"name":"Department of Medicine and Department of Laboratory Medicine, University of California, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel D.","family":"Ernst","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026070402051809000_2026.06.25.734601v1.1","unstructured":"Global Tuberculosis Report 2025. 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