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A novel therapeutic strategy of lipidated promiscuous peptide against Mycobacterium tuberculosis by eliciting Th1 and Th17 immunity of host.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title A novel therapeutic strategy of lipidated promiscuous peptide against Mycobacterium tuberculosis by eliciting Th1 and Th17 immunity of host.
 
Creator Rai, Pradeep K
Chodisetti, Sathi Babu
Nadeem, Sajid
Maurya, Sudeep K
Gowthaman, Uthaman
Zeng, Weiguang
Janmeja, Ashok Kumar
Jackson, David C
Agrewala, J N
 
Subject QR180 Immunology
 
Description Regardless of the fact that potent drug-regimen is currently available, tuberculosis continues to kill 1.5 million people annually. Tuberculosis patients are not only inflicted by the trauma of disease but they also suffer from the harmful side-effects, immune suppression and drug resistance instigated by prolonged therapy. It is an exigency to introduce radical changes in the existing drug-regime and discover safer and better therapeutic measures. Hence, we designed a novel therapeutic strategy by reinforcing the efficacy of drugs to kill Mtb by concurrently boosting host immunity by L91. L91 is chimera of promiscuous epitope of Acr1 antigen of Mtb and TLR-2 agonist Pam2Cys. The adjunct therapy using drugs and L91 (D-L91) significantly declined the bacterial load in Mtb infected animals. The mechanism involved was through enhancement of IFN-γ(+)TNF-α(+) polyfunctional Th1 cells and IL-17A(+)IFN-γ(+) Th17 cells, enduring memory CD4 T cells and downregulation of PD-1. The down-regulation of PD-1 prevents CD4 T cells from undergoing exhaustion and improves their function against Mtb. Importantly, the immune response observed in animals could be replicated using T cells of tuberculosis patients on drug therapy. In future, D-L91 therapy can invigorate drugs potency to treat tuberculosis patients and reduce the dose and duration of drug-regime.
 
Publisher Nature publishing group
 
Date 2016
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/1846/1/69.pdf
Rai, Pradeep K and Chodisetti, Sathi Babu and Nadeem, Sajid and Maurya, Sudeep K and Gowthaman, Uthaman and Zeng, Weiguang and Janmeja, Ashok Kumar and Jackson, David C and Agrewala, J N (2016) A novel therapeutic strategy of lipidated promiscuous peptide against Mycobacterium tuberculosis by eliciting Th1 and Th17 immunity of host. Scientific reports, 6. ISSN 2045-2322 (In Press)
 
Relation http://www.nature.com/articles/srep23917
http://crdd.osdd.net/open/1846/