{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:15:38Z","timestamp":1787026538022,"version":"build-2736575974"},"reference-count":72,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"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>Objective<\/jats:title>\n                    <jats:p>\n                      Cysteamine, a drug approved to treat cystinosis, has been proposed as a host-directed therapy for\n                      <jats:italic>M. tuberculosis<\/jats:italic>\n                      (Mtb) and SARS-CoV-2. The impact of cysteamine on the immune responses has not been fully investigated. We aimed to\n                      <jats:italic>in vitro<\/jats:italic>\n                      evaluate the immunomodulatory effects of cysteamine on peripheral blood mononuclear cells (PBMCs) using the purified protein derivative (PPD) as a recall antigen, and an unspecific stimulus as staphylococcal enterotoxin B (SEB).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      PBMCs isolated from subjects with tuberculosis infection (TBI), those with tuberculosis disease (TB), and healthy controls (HC) were\n                      <jats:italic>in vitro<\/jats:italic>\n                      stimulated with PPD or SEB and treated or not with cysteamine at different concentrations (50 \u00b5M\u2013400 \u00b5M) for 6 hours (h) and 24 h. We evaluated the T helper1 (Th1) and T cytotoxic1 (Tc1) cell cytokine production by flow cytometry and immune-enzymatic assays. In HC, we also evaluated apoptosis and\/or necrosis by flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We observed an immunomodulatory effect of cysteamine at 400 \u00b5M in PBMCs from TB and TBI subjects. It significantly reduced PPD-specific Th1 responses at 24 h and at 6 h (p=0.0004 and p=0.0009, respectively), and a similar non-significant trend was observed with cysteamine at 200 \u00b5M (p=0.06 at 24 h and p=0.14 at 6 h). Moreover, cysteamine at both 400 \u00b5M (p&amp;lt;0.0001 and p=0.0187 at 24 h, respectively, and p&amp;lt;0.0001 at 6 h for both) and 200 \u00b5M (p=0.0119 and p=0.0028 at 24 h and p=0.0028 and p=0.0003 at 6 h, respectively) significantly reduced SEB-induced Th1 and Tc1 responses. Furthermore, we found that cysteamine induced morphological lymphocyte changes and significantly reduced the lymphocyte percentage in a dose- and time-dependent manner. Cysteamine at 400 \u00b5M induced 8% late apoptosis and 1.6% necrosis (p&amp;lt;0.05) at 24 h. In contrast, despite significant differences from untreated conditions (p&amp;lt;0.05), cysteamine at 400 \u00b5M for 6 h induced approximately 1% late apoptosis and 0.1% necrosis in the cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      High doses of cysteamine\n                      <jats:italic>in vitro<\/jats:italic>\n                      reduce the percentages of PPD- and SEB-induced Th1 and Tc1 cells and induce late apoptosis and necrosis. Differently, cysteamine at lower doses retains the immunomodulatory effect without affecting cell viability. These findings suggest cysteamine as a potential adjunct to antimicrobial regimens as in the TB or COVID-19 field, for its ability to reduce the inflammatory status.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2024.1411827","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:38:29Z","timestamp":1730075909000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Immunomodulatory effects of cysteamine and its potential use as a host-directed therapy for 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