{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T14:58:55Z","timestamp":1793977135558,"version":"4.8.0"},"reference-count":156,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tuberculosis (TB) remains a leading cause of infectious disease mortality worldwide, and the rising prevalence of diabetes mellitus (DM) represents a major obstacle to TB control. DM increases susceptibility to TB, worsens disease severity, delays treatment response, and is associated with poorer outcomes, largely through disruption of host immunity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a systematic review of studies published between 1974 and May 31, 2023 that examined immunological mechanisms through which DM alters TB pathogenesis. In total, 81 eligible studies involving animal models, human participants, or combined approaches were identified and synthesised across different stages of TB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Across studies, DM was associated with broad dysregulation of innate and adaptive immune responses, altered cytokine signalling, impaired granuloma structure and function, and reduced control of\n                      <jats:italic>Mycobacterium tuberculosis (Mtb)<\/jats:italic>\n                      . Distinct immune profiles emerged between TB disease with DM and latent TB infection with DM, with heterogeneity partly explained by differences in study design, metabolic status, and disease stage. Importantly, emerging evidence indicates that pre-diabetes and intermediate hyperglycaemia may also compromise TB immunity and contribute to disease progression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings highlight DM as a key immunometabolic modifier of TB pathogenesis. They also suggest that earlier metabolic optimisation and host-directed therapeutic strategies could be explored as potential approaches to improve outcomes in this growing high-risk TB-DM population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/<\/jats:ext-link>\n                      , identifier CRD42023431040.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1803046","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:22:09Z","timestamp":1776918129000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Immune dysregulation in tuberculosis-diabetes comorbidity: mechanistic and translational insights"],"prefix":"10.3389","volume":"17","author":[{"given":"Aminat Y.","family":"Saula","sequence":"first","affiliation":[{"name":"Centre for Mathematical Biology, Department of Mathematical Sciences, University of Bath","place":["Claverton Down, Bath, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muge","family":"Cevik","sequence":"additional","affiliation":[{"name":"Division of Infection and Global Health Research, School of Medicine, University of St Andrews","place":["St Andrews, Scotland, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline M.","family":"Cliff","sequence":"additional","affiliation":[{"name":"Centre of Inflammation Research and Translational Medicine, and Department of Biosciences, Brunel University of London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Ronacher","sequence":"additional","affiliation":[{"name":"Translational Research Institute, Mater Research Institute, The University of Queensland","place":["Brisbane, QLD, Australia"]},{"name":"Australian Infectious Diseases Research Centre, The University of Queensland","place":["Brisbane, QLD, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Bowness","sequence":"additional","affiliation":[{"name":"Centre for Mathematical Biology, Department of Mathematical Sciences, University of Bath","place":["Claverton Down, Bath, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"B1","unstructured":"Tuberculosis: key facts\n          \n          \n          \n          2024"},{"key":"B2","unstructured":"Tuberculosis: key facts\n          \n          \n     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