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RESEARCH PRODUCT
Phenolic-glycolipid-1 and lipoarabinomannan preferentially modulate TCR- and CD28-triggered proximal biochemical events, leading to T-cell unresponsiveness in mycobacterial diseases
Arshad RizviNaim Akhtar KhanBhawna SharmaVishwa Mohan KatochRajni UpadhyayBhavyata DuaBeenu JoshiPradeep K. DagurPradeep K. DagurUtpal Senguptasubject
LipopolysaccharidesEndocrinology Diabetes and MetabolismT-LymphocytesClinical BiochemistryPGL-1Man-LAMGene ExpressionLymphocyte ActivationJurkat cellsJurkat CellsEndocrinologyT-cell activationIL-2 receptorPhosphorylationExtracellular Signal-Regulated MAP KinasesPromoter Regions Geneticlcsh:RC620-627Protein Kinase CImmunity CellularZAP-70 Protein-Tyrosine KinaseCD28hemic and immune systemsCell biologyMycobacterium lepraelcsh:Nutritional diseases. Deficiency diseasesmedicine.anatomical_structureHost-Pathogen InteractionsProtein BindingMAP Kinase Signaling SystemT cellReceptors Antigen T-Cellchemical and pharmacologic phenomenaBiologyImmune systemCD28 AntigensLeprosymedicineHumansSecretionCalcium SignalingCell ProliferationBiochemistry medicalAntigens BacterialLipoarabinomannanNFATC Transcription FactorsResearchBiochemistry (medical)T-cell receptorInterleukin-2 Receptor alpha SubunitMycobacteriaGene Expression RegulationAnergyImmunologyLeukocytes MononuclearInterleukin-2Glycolipidsdescription
Abstract 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-09-01 | Lipids in Health and Disease |