{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T21:08:22Z","timestamp":1789074502875,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,8]]},"group-title":"Immunology","reference-count":56,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH\/NIAID","award":["R01AI155621"],"award-info":[{"award-number":["R01AI155621"]}]},{"name":"NIH\/NIAID","award":["R01AI179037"],"award-info":[{"award-number":["R01AI179037"]}]},{"name":"NIH\/NIAID","award":["F31AI197727"],"award-info":[{"award-number":["F31AI197727"]}]},{"name":"NIH\/NIAID","award":["F31AI176652"],"award-info":[{"award-number":["F31AI176652"]}]},{"name":"NIH\/NIAID","award":["F31AI176795"],"award-info":[{"award-number":["F31AI176795"]}]},{"name":"NIH\/NIAID","award":["F31CA298557"],"award-info":[{"award-number":["F31CA298557"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Myeloid cells are essential mediators of host defense against\n                  <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                  (Mtb), yet the metabolic programs that sustain their function during chronic infection remain poorly defined. Here, using scRNA-seq we identified a striking, coordinated decline in mitochondrial electron transport chain gene expression across diverse myeloid populations as Mtb disease progressed in mice. This transcriptional remodeling was associated with broad changes in immune and metabolic pathways, including reduced antigen presentation, interferon responses, protein synthesis, and glycolysis. Accordingly, loss of Complex I in macrophages (\n                  <jats:italic>Ndufs4<\/jats:italic>\n                  knockdown) reduced MHC-II surface expression, dysregulated inflammatory gene expression, and limited control of Mtb replication. Finally, analysis of single-cell transcriptomic data from Mtb-exposed human household contacts identified an almost identical transcriptional program enriched in IGRA+ individuals, supporting a role for mitochondrial respiratory remodeling in human TB. Together, these findings demonstrate that mitochondrial bioenergetic competence is required to sustain macrophage effector function during chronic Mtb infection and suggest that mitochondrial restoration may boost protective responses in TB patients.\n                <\/jats:p>","DOI":"10.64898\/2026.09.04.749543","type":"posted-content","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:25:12Z","timestamp":1788931512000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss of Mitochondrial Respiratory Capacity Reshapes Myeloid Cell Function during\n                  <i>Mycobacterium tuberculosis<\/i>\n                  infection"],"prefix":"10.64898","author":[{"given":"Eduardo L.","family":"Martinez","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory J.","family":"Mabry","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M University, Naresh K. Vashist College of Medicine, Bryan, TX 77807, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aja K.","family":"Coleman","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M University, Naresh K. Vashist College of Medicine, Bryan, TX 77807, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan S.","family":"Osborne","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Simmons","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica B.","family":"Huskey","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Division of Molecular Pathogenesis, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn S.","family":"Armijo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Division of Molecular Pathogenesis, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Newbolt","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob R.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianna","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious 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