{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T05:52:37Z","timestamp":1791352357685,"version":"4.3.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"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>Chromoblastomycosis (CBM) is a chronic, neglected tropical fungal infection. Its immunopathogenesis, particularly the mechanism underlying its chronicity, remains poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed single-cell RNA sequencing (scRNA-seq) on lesional skin from a CBM patient, followed by comprehensive bioinformatics analyses. We then used multiplex immunofluorescence (mIF) to validate CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell exhaustion in CBM patient lesions and the mouse model of\n                      <jats:italic>Fonsecaea pedrosoi<\/jats:italic>\n                      infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a significantly expanded population of exhausted CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells within the patient\u2019s lesions, which exhibited high co-expression of inhibitory receptors (PD-1, TIM-3, LAG-3) and functional impairment. Trajectory inference suggested a differentiation path from naive towards exhaustion within the chronic inflammatory environment. Cell-cell communication analysis implicated monocytes\/macrophages (MoMacs) as key drivers of this process via persistent antigen presentation and ligand-receptor interactions such as CTLA4-CD80\/86 and LGALS9-CD44. The accumulation of exhausted CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells was confirmed in human CBM lesions by multiplex immunofluorescence (mIF), and the progressive development of exhaustion was recapitulated in the mouse model of\n                      <jats:italic>Fonsecaea pedrosoi<\/jats:italic>\n                      infection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Our findings establish CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cell exhaustion as an important mechanism underlying the chronicity of chromoblastomycosis, revealing a new immunopathological perspective for this neglected disease.\n                    <\/jats:p>\n                  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