Immunotherapeutic Role of NOD-2 and TLR-4 Signaling as an Adjunct to Antituberculosis Chemotherapy

ACS Infect Dis. 2021 Nov 12;7(11):2999-3008. doi: 10.1021/acsinfecdis.1c00136. Epub 2021 Oct 6.

Abstract

Tuberculosis (TB) treatment is lengthy and inflicted with severe side-effects. Here, we attempted a novel strategy to reinforce host immunity through NOD-like receptor (NOD-2) and Toll-like receptor (TLR-4) signaling in the murine model of TB. Intriguingly, we noticed that it not only bolstered the immunity but also reduced the dose and duration of rifampicin and isoniazid therapy. Further, we observed expansion in the pool of effector (CD44hi, CD62Llo, CD127hi) and central (CD44hi, CD62Lhi, CD127hi) memory CD4 T cells and CD8 T cells and increased the intracellular killing of Mycobacterium tuberculosis (Mtb) by activated dendritic cells [CD86hi, CD40hi, IL-6hi, IL-12hi, TNF-αhi, nitric oxide (NO)hi] with significant reduction in Mtb load in the lungs and spleen of infected animals. We infer that the signaling through NOD-2 and TLR-4 may be an important approach to reduce the dose and duration of the drugs to treat TB.

Keywords: Mycobacterium tuberculosis; antibiotics; host-directed therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitubercular Agents / pharmacology
  • Immunotherapy
  • Mice
  • Mycobacterium tuberculosis*
  • Nod2 Signaling Adaptor Protein* / immunology
  • Toll-Like Receptor 4* / genetics
  • Toll-Like Receptor 4* / immunology
  • Toll-Like Receptors

Substances

  • Antitubercular Agents
  • Nod2 Signaling Adaptor Protein
  • Nod2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Toll-Like Receptors