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Phenolic-glycolipid-1 and lipoarabinomannan preferentially modulate TCR- and CD28-triggered proximal biochemical events, leading to T-cell unresponsiveness in mycobacterial diseases
BACKGROUND: Advanced stages of leprosy show T cell unresponsiveness and lipids of mycobacterial origin are speculated to modulate immune responses in these patients. Present study elucidates the role of phenolicglycolipid (PGL-1) and Mannose-capped lipoarabinomannan (Man-LAM) on TCR- and TCR/CD28- m...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477116/ https://www.ncbi.nlm.nih.gov/pubmed/22985026 http://dx.doi.org/10.1186/1476-511X-11-119 |
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author | Dagur, Pradeep Kumar Sharma, Bhawna Upadhyay, Rajni Dua, Bhavyata Rizvi, Arshad Khan, Naim Akhtar Katoch, Vishwa Mohan Sengupta, Utpal Joshi, Beenu |
author_facet | Dagur, Pradeep Kumar Sharma, Bhawna Upadhyay, Rajni Dua, Bhavyata Rizvi, Arshad Khan, Naim Akhtar Katoch, Vishwa Mohan Sengupta, Utpal Joshi, Beenu |
author_sort | Dagur, Pradeep Kumar |
collection | PubMed |
description | BACKGROUND: Advanced stages of leprosy show T cell unresponsiveness and lipids of mycobacterial origin are speculated to modulate immune responses in these patients. Present study elucidates the role of phenolicglycolipid (PGL-1) and Mannose-capped lipoarabinomannan (Man-LAM) on TCR- and TCR/CD28- mediated signalling. RESULTS: We observed that lipid antigens significantly inhibit proximal early signalling events like Zap-70 phosphorylation and calcium mobilization. Interestingly, these antigens preferentially curtailed TCR-triggered early downstream signalling events like p38 phosphorylation whereas potentiated that of Erk1/2. Further, at later stages inhibition of NFAT binding, IL-2 message, CD25 expression and T-cell blastogenesis by PGL-1 and Man-LAM was noted. CONCLUSION: Altogether, we report that Man-LAM and PGL-1 preferentially interfere with TCR/CD28-triggered upstream cell signalling events, leading to reduced IL-2 secretion and T-cell blastogenesis which potentially could lead to immunosupression and thus, disease exacerbation, as noted in disease spectrum. |
format | Online Article Text |
id | pubmed-3477116 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-34771162012-10-22 Phenolic-glycolipid-1 and lipoarabinomannan preferentially modulate TCR- and CD28-triggered proximal biochemical events, leading to T-cell unresponsiveness in mycobacterial diseases Dagur, Pradeep Kumar Sharma, Bhawna Upadhyay, Rajni Dua, Bhavyata Rizvi, Arshad Khan, Naim Akhtar Katoch, Vishwa Mohan Sengupta, Utpal Joshi, Beenu Lipids Health Dis Research BACKGROUND: Advanced stages of leprosy show T cell unresponsiveness and lipids of mycobacterial origin are speculated to modulate immune responses in these patients. Present study elucidates the role of phenolicglycolipid (PGL-1) and Mannose-capped lipoarabinomannan (Man-LAM) on TCR- and TCR/CD28- mediated signalling. RESULTS: We observed that lipid antigens significantly inhibit proximal early signalling events like Zap-70 phosphorylation and calcium mobilization. Interestingly, these antigens preferentially curtailed TCR-triggered early downstream signalling events like p38 phosphorylation whereas potentiated that of Erk1/2. Further, at later stages inhibition of NFAT binding, IL-2 message, CD25 expression and T-cell blastogenesis by PGL-1 and Man-LAM was noted. CONCLUSION: Altogether, we report that Man-LAM and PGL-1 preferentially interfere with TCR/CD28-triggered upstream cell signalling events, leading to reduced IL-2 secretion and T-cell blastogenesis which potentially could lead to immunosupression and thus, disease exacerbation, as noted in disease spectrum. BioMed Central 2012-09-17 /pmc/articles/PMC3477116/ /pubmed/22985026 http://dx.doi.org/10.1186/1476-511X-11-119 Text en Copyright ©2012 Dagur et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Dagur, Pradeep Kumar Sharma, Bhawna Upadhyay, Rajni Dua, Bhavyata Rizvi, Arshad Khan, Naim Akhtar Katoch, Vishwa Mohan Sengupta, Utpal Joshi, Beenu Phenolic-glycolipid-1 and lipoarabinomannan preferentially modulate TCR- and CD28-triggered proximal biochemical events, leading to T-cell unresponsiveness in mycobacterial diseases |
title | Phenolic-glycolipid-1 and lipoarabinomannan preferentially modulate TCR- and CD28-triggered proximal biochemical events, leading to T-cell unresponsiveness in mycobacterial diseases |
title_full | Phenolic-glycolipid-1 and lipoarabinomannan preferentially modulate TCR- and CD28-triggered proximal biochemical events, leading to T-cell unresponsiveness in mycobacterial diseases |
title_fullStr | Phenolic-glycolipid-1 and lipoarabinomannan preferentially modulate TCR- and CD28-triggered proximal biochemical events, leading to T-cell unresponsiveness in mycobacterial diseases |
title_full_unstemmed | Phenolic-glycolipid-1 and lipoarabinomannan preferentially modulate TCR- and CD28-triggered proximal biochemical events, leading to T-cell unresponsiveness in mycobacterial diseases |
title_short | Phenolic-glycolipid-1 and lipoarabinomannan preferentially modulate TCR- and CD28-triggered proximal biochemical events, leading to T-cell unresponsiveness in mycobacterial diseases |
title_sort | phenolic-glycolipid-1 and lipoarabinomannan preferentially modulate tcr- and cd28-triggered proximal biochemical events, leading to t-cell unresponsiveness in mycobacterial diseases |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3477116/ https://www.ncbi.nlm.nih.gov/pubmed/22985026 http://dx.doi.org/10.1186/1476-511X-11-119 |
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