Supplementary Material for: NOD-2 and TLR-4 Signaling Reinforces the Efficacy of Dendritic Cells and Reduces the Dose of TB Drugs against <b><i>Mycobacterium tuberculosis</i></b>

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 <i>Mycobacterium tuberculosis</i><i>(Mtb)</i> 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 <i>Mtb</i>. 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 <i>Mtb</i> 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.