AUTHOR=Aqdas Mohammad , Singh Sanpreet , Amir Mohammed , Maurya Sudeep Kumar , Pahari Susanta , Agrewala Javed Naim TITLE=Cumulative Signaling Through NOD-2 and TLR-4 Eliminates the Mycobacterium Tuberculosis Concealed Inside the Mesenchymal Stem Cells JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 11 - 2021 YEAR=2021 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.669168 DOI=10.3389/fcimb.2021.669168 ISSN=2235-2988 ABSTRACT=Since long, tuberculosis (TB) has been inflicting mankind with highest morbidity and mortality. Although, the current treatment is extremely potent, yet few bacilli can still hide inside the host mesenchymal stem cells (MSC). Functional capabilities of MSCs are known to be modulated by TLRs, NOD-2 and RIG-1 signaling. Therefore, we hypothesize that modulating the MSC activity through TLR-4 and NOD-2 can be an attractive immunotherapeutic strategy against Mtb. In our current study, we observed that MSC stimulated through TLR-4 and NOD-2 (N2.T4) i) activated MSC and augmented the secretion of pro-inflammatory cytokines; ii) co-localized Mtb¬ in the lysosomes; iii) induced autophagy; iv) enhanced NF-κB activity via p38 MAPK signaling pathway; v) significantly reduced the intracellular Mtb¬ survival. Overall, the results suggest that the triggering through N2.T4 can be a future immunotherapy to eliminate the Mtb¬ concealed inside the MSC.