Immunomodulatory effects of cysteamine and its potential use as a host-directed therapy for tuberculosis
Cysteamine, a drug approved to treat cystinosis, has been proposed as a host-directed therapy for (Mtb) and SARS-CoV-2. The impact of cysteamine on the immune responses has not been fully investigated. We aimed to evaluate the immunomodulatory effects of cysteamine on peripheral blood mononuclear ce...
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| Published in: | Frontiers in immunology Vol. 15; p. 1411827 |
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| Main Authors: | , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Switzerland
Frontiers Media SA
28.10.2024
Frontiers Media S.A |
| Subjects: | |
| ISSN: | 1664-3224, 1664-3224 |
| Online Access: | Get full text |
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| Summary: | Cysteamine, a drug approved to treat cystinosis, has been proposed as a host-directed therapy for
(Mtb) and SARS-CoV-2. The impact of cysteamine on the immune responses has not been fully investigated. We aimed to
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).
PBMCs isolated from subjects with tuberculosis infection (TBI), those with tuberculosis disease (TB), and healthy controls (HC) were
stimulated with PPD or SEB and treated or not with cysteamine at different concentrations (50 µM-400 µM) 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.
We observed an immunomodulatory effect of cysteamine at 400 µM 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 µM (p=0.06 at 24 h and p=0.14 at 6 h). Moreover, cysteamine at both 400 µM (p<0.0001 and p=0.0187 at 24 h, respectively, and p<0.0001 at 6 h for both) and 200 µM (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 µM induced 8% late apoptosis and 1.6% necrosis (p<0.05) at 24 h. In contrast, despite significant differences from untreated conditions (p<0.05), cysteamine at 400 µM for 6 h induced approximately 1% late apoptosis and 0.1% necrosis in the cells.
High doses of cysteamine
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. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Anuradha Rajamanickam, International Centers for Excellence in Research (ICER), India Reviewed by: Palmira Barreira-Silva, University of Porto, Portugal These authors have contributed equally to this work and share first authorship Edited by: Mohlopheni Jackson Marakalala, Africa Health Research Institute (AHRI), South Africa |
| ISSN: | 1664-3224 1664-3224 |
| DOI: | 10.3389/fimmu.2024.1411827 |