{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:18:30Z","timestamp":1789525110428,"version":"build-2803163510"},"posted":{"date-parts":[[2025,10,6]]},"group-title":"Immunology","reference-count":57,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 AI051242"],"award-info":[{"award-number":["R01 AI051242"]}]},{"name":"NIH","award":["U01 AI166309"],"award-info":[{"award-number":["U01 AI166309"]}]},{"name":"NIH","award":["P30 AI168440"],"award-info":[{"award-number":["P30 AI168440"]}]},{"name":"NIH","award":["R25 AI147375"],"award-info":[{"award-number":["R25 AI147375"]}]},{"name":"NIH","award":["F31 AI172360"],"award-info":[{"award-number":["F31 AI172360"]}]},{"name":"NIH","award":["F32 HL162424"],"award-info":[{"award-number":["F32 HL162424"]}]},{"name":"NIH","award":["T32 HL007185"],"award-info":[{"award-number":["T32 HL007185"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Lung mononuclear phagocyte (MNP) subsets differ in their ability to restrict\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  (Mtb) during chronic infection, yet the mechanisms underlying this difference are not well defined. Here, we show that CD11c\n                  <jats:sup>lo<\/jats:sup>\n                  monocyte-derived cells (MNC1), the subset of lung cells that is most permissive for Mtb viability during chronic infection, express lower levels of interferon-gamma (IFN\u03b3) signaling proteins, resulting in reduced responses to IFN\u03b3 compared to alveolar macrophages (AM) and CD11c\n                  <jats:sup>hi<\/jats:sup>\n                  MNC2. Moreover, type I IFN signaling suppresses IFN\u03b3-mediated MHC-II expression, impairing antigen-specific CD4 T cell activation by MNC1 cells. Importantly, prior immunity conferred by contained Mtb infection enhances IFN\u03b3 responsiveness of monocyte-derived cells, reducing bacterial burdens in lungs and within MNC subsets. Our findings indicate that heterogeneous IFN\u03b3 responsiveness is exploited by Mtb for persistence in vivo. Overcoming or bypassing impaired IFN\u03b3 responsiveness may guide the development of more effective TB vaccines and host-directed therapies.\n                <\/jats:p>","DOI":"10.1101\/2025.10.06.680719","type":"posted-content","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T02:40:13Z","timestamp":1759804813000},"source":"Crossref","is-referenced-by-count":5,"title":["Impaired IFN\u03b3 responsiveness of monocyte-derived lung cells limits immunity to\n                  <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8038-1207","authenticated-orcid":false,"given":"Weihao","family":"Zheng","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\/0000-0002-7893-8416","authenticated-orcid":false,"given":"Jason 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