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NOD-2 and TLR-4 Signaling Reinforces the Efficacy of Dendritic Cells and Reduces the Dose of TB Drugs against Mycobacterium tuberculosis.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title NOD-2 and TLR-4 Signaling Reinforces the Efficacy of Dendritic Cells and Reduces the Dose of TB Drugs against Mycobacterium tuberculosis.
 
Creator Khan, Nargis
Pahari, Susanta
Vidyarthi, Aurobind
Aqdas, Mohammad
Agrewala, Javed N
 
Subject QR Microbiology
 
Description Tuberculosis (TB) is one of the leading killer infectious diseases. TB patients are inflicted with devastating side effects and the toxicity of a lengthy drug regime, accentuating an urgent need to explore newer and safer treatment methods. Recently, an improved understanding of host-pathogen interaction has opened new avenues for TB treatment, including immunotherapy. This has emboldened us to devise a novel strategy to restrict Mycobacterium tuberculosis(Mtb) growth by activating dendritic cells (DCs) through the NOD-2 and TLR-4 molecules of innate immunity. Triggered DCs show a robust release of cytokines and nitric oxide, autophagy and improved migration towards the lymph nodes, and consequently impede the intracellular survival of Mtb. Of note, this approach enhanced the efficacy of TB drugs by reducing their dose to a 5-fold lesser concentration than recommended. In vivo administration of ligands of NOD-2 (NOD-2L) and TLR-4 (TLR-4L) substantially increased the pool of effector memory CD4 and CD8 T cells. Additionally, NOD-2L and TLR-4L, in conjunction with the reduced dose of isoniazid, substantially declined the Mtb burden in the lungs. In the future, adjunct therapy involving NOD-2L, TLR-4L and TB drugs may have enough potential to reduce the dose and duration of treatment of TB patients.
 
Publisher Karger AG, Basel
 
Date 2015-11-28
 
Type Article
PeerReviewed
 
Relation http://www.karger.com/Article/Abstract/439591
http://crdd.osdd.net/open/1736/
 
Identifier Khan, Nargis and Pahari, Susanta and Vidyarthi, Aurobind and Aqdas, Mohammad and Agrewala, Javed N (2015) NOD-2 and TLR-4 Signaling Reinforces the Efficacy of Dendritic Cells and Reduces the Dose of TB Drugs against Mycobacterium tuberculosis. Journal of innate immunity. ISSN 1662-8128