{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:12:56Z","timestamp":1788415976119,"version":"build-2803163510"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"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>Introduction<\/jats:title>\n                    <jats:p>\n                      This study establishes and characterizes a novel experimental mouse model to evaluate\n                      <jats:italic>Sporothrix brasiliensis<\/jats:italic>\n                      infection under type 1 diabetic conditions, providing a comprehensive description of the associated clinicopathological and immunometabolic alterations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Diabetic and normoglycemic control mice were infected with\n                      <jats:italic>S. brasiliensis<\/jats:italic>\n                      to evaluate clinical progression, fungal dissemination, mortality, systemic cytokines, splenic T cell subsets, macrophage functional responses, and hepatic autophagic markers (\n                      <jats:italic>p62\/SQSTM1<\/jats:italic>\n                      , Beclin-1, and LC3B-II).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Diabetic mice exhibited enhanced susceptibility to infection compared to normoglycemic controls, presenting with progressive ulcerative lesions, systemic dissemination (lymph nodes, liver, and brain), and 100% mortality. This severe phenotype was accompanied by a dysregulated inflammatory profile, characterized by elevated systemic TNF-\u03b1, IFN-\u03b3, and IL-6 alongside reduced splenic CD4+ T cell frequencies. Functionally, macrophages from diabetic hosts displayed an initial increase in yeast association followed by a rapid decline, consistent with cellular exhaustion. Additionally, infected diabetic mice exhibited hepatic accumulation of\n                      <jats:italic>p62\/SQSTM1<\/jats:italic>\n                      without alterations in Beclin-1 or LC3B-II, suggesting potential disruption during late-stage autophagic clearance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Overall, this model successfully reproduces severe, disseminated sporotrichosis under hyperglycemic conditions and delineates the multifaceted immune dysregulation associated with host susceptibility. This novel experimental platform provides a valuable tool for future studies exploring fungal pathogenesis and therapeutic strategies in metabolic comorbidities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1902740","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:17:47Z","timestamp":1788412667000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Diabetes impairs antifungal immunity and drives fatal disseminated sporotrichosis in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Mariana Araujo","family":"Oliveira","sequence":"first","affiliation":[{"name":"Laboratory of Immunoendocrinology, Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S\u00e3o Paulo","place":["S\u00e3o Paulo, Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ywa Perp\u00e9tuo Socorro 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