{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:52:20Z","timestamp":1786467140810,"version":"build-2736575974"},"reference-count":52,"publisher":"National Academy of Sciences","issue":"33","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"HHS | NIH | NIAID | Division of Intramural Research","doi-asserted-by":"publisher","award":["AI134245 AI181701 and AI128130 to SM AI111914 AI134240 AI138587 and AI184581 to DK and by instit"],"award-info":[{"award-number":["AI134245 AI181701 and AI128130 to SM AI111914 AI134240 AI138587 and AI184581 to DK and by instit"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005445","name":"NSF | BFA | Division of Grants and Agreements","doi-asserted-by":"publisher","award":["2017242837) and training grant 5T32AI007290"],"award-info":[{"award-number":["2017242837) and training grant 5T32AI007290"]}],"id":[{"id":"10.13039\/100005445","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:p>\n                    Granulomas, the hallmark of tuberculosis (TB) disease, can both restrict\n                    <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                    ) dissemination and impede its clearance. Recent studies indicate that indoleamine 2,3-dioxygenase (IDO1), an immunosuppressive metabolic enzyme, limits infiltration of activated T cells and can contribute to TB disease progression. Treatment with 1-methyl-D-tryptophan (D-1MT), a small molecule inhibitor that restores mTOR signaling, has been shown to reduce IDO1 activity and improve immune responses in\n                    <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                    -infected rhesus macaques. Here, we investigated the impact of D-1MT treatment on TB granuloma architecture using 30-plex high-dimensional issue imaging in rhesus macaques. By spatially mapping 13 distinct cell populations, we found D-1MT treatment corresponded with significantly increased infiltration CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells into granulomas compared to untreated controls. Notably, these CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells expressed markers of cell proliferation and cytotoxicity. D-1MT enhanced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration throughout the granuloma, with particularly pronounced effects in the myeloid core, where we observed significantly enhanced spatial interactions between macrophages and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, but not CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Our results demonstrate that: i) effective intragranulomatous\n                    <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                    control is associated with the close spatial proximity between CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and macrophages, a feature less abundant in uncontrolled pulmonary TB; ii) IDO1 induction blocks CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration and reduces T cell activation and proliferation; and iii) therapeutic strategies, including D-1MT, that improve intragranulomatous killing hold strong translational potential.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2528104123","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:07:56Z","timestamp":1786464476000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic remodeling of the tuberculosis granuloma with 1-methyl-D-tryptophan enhances CD8\n                    <sup>+<\/sup>\n                    T cell\u2013macrophage interactions"],"prefix":"10.1073","volume":"123","author":[{"given":"Erin F.","family":"McCaffrey","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00f54p054","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, Stanford University School of Medicine","place":["Stanford"]},{"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}],"name":"Spatial Immunology Unit, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health","place":["Bethesda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alea C.","family":"Delmastro","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00f54p054","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, Stanford University School 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F. McCaffrey . angelolab\/publications. GitHub. https:\/\/github.com\/angelolab\/publications\/tree\/main\/2025-McCaffrey-Delmastro_etal_D1MT. Deposited 26 September 2025."},{"key":"e_1_3_4_52_2","doi-asserted-by":"crossref","unstructured":"E. F. McCaffrey . Therapeutic remodeling of the tuberculosis granuloma with 1-methyl-D-tryptophan enhances CD8+ T cell-macrophage interactions. Mendeley Data. https:\/\/data.mendeley.com\/datasets\/x5sf8gpr67\/1. 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