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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...

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Autores principales: Dagur, Pradeep Kumar, Sharma, Bhawna, Upadhyay, Rajni, Dua, Bhavyata, Rizvi, Arshad, Khan, Naim Akhtar, Katoch, Vishwa Mohan, Sengupta, Utpal, Joshi, Beenu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
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.
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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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