4-(Benzyloxy)phenol-induced p53 exhibits antimycobacterial response triggering phagosome-lysosome fusion through ROS-dependent intracellular Ca pathway in THP-1 cells.

Drug-resistant tuberculosis (TB) outbreak has emerged as a global public health crisis. Therefore, new and innovative therapeutic options like host-directed therapies (HDTs) through novel modulators are urgently required to overcome the challenges associated with TB. In the present study, we have investigated the anti-mycobacterial effect of 4-(Benzyloxy)phenol.

Soybean lectin-triggered IL-6 secretion induces autophagy to kill intracellular mycobacteria through P2RX7 dependent activation of the JAK2/STAT3/Mcl-1 pathway.

Cytokine therapy and cytokine-mediated autophagy have been used as prominent host-directed therapy (HDT) approaches to restrain M. tb growth in the host cell. In the present study, we have dissected the anti-tubercular activity of Soybean lectin (SBL) through cytokine-mediated autophagy induction in differentiated THP-1 (dTHP-1) cells.

Involvement of epigenetics in affecting host immunity during SARS-CoV-2 infection.

Coronavirus disease 19 (COVID-19) is caused by a highly contagious RNA virus Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), originated in December 2019 in Wuhan, China. Since then, it has become a global public health concern and leads the disease table with the highest mortality rate, highlighting the necessity for a thorough understanding of its biological properties. The intricate interaction between the virus and the host immune system gives rise to diverse implications of COVID-19.

ESAT-6 impedes IL-18 mediated phagosome lysosome fusion via microRNA-30a upon Calcimycin treatment in mycobacteria infected macrophages.

The weaponry possessed by Mycobacterium tuberculosis (M. tb) in the form of immunodominant antigens hijack the host immune system to give a survival advantage to this intracellular fiend, but the mechanism of this control is not entirely known. Since we have previously reported the mechanism of autophagy inhibition by early secreted antigenic target 6 kDa (ESAT-6) through microRNA (miR)-30a-3p in Calcimycin treated differentiated THP-1 (dTHP-1) cells, the present study was undertaken to deduce the effect of miR-30a on the immunomodulatory profile of ESAT-6 treated cells and the mechanism involved thereof, if any.

P2X7 receptor in multifaceted cellular signalling and its relevance as a potential therapeutic target in different diseases.

P2X7 receptor, a purinergic receptor family member, is abundantly expressed on many cells, including immune, muscle, bone, neuron, and glia. It acts as an ATP-activated cation channel that permits the influx of Ca, Na and efflux of K ions. The P2X7 receptor plays crucial roles in many physiological processes including cytokine and chemokine secretion, NLRP3 inflammasome activation, cellular growth and differentiation, locomotion, wound healing, transcription factors activation, cell death and T-lymphocyte survival.

Soybean lectin induces autophagy through P2RX7 dependent activation of NF-κB-ROS pathway to kill intracellular mycobacteria.

Background: Host-directed therapy is considered a novel anti-tuberculosis strategy in tackling the tuberculosis burden through autophagy induction by various inducers to curtail the growth of intracellular Mycobacterium tuberculosis.

Methods: In this study, we investigated the anti-tubercular role of soybean lectin, a lectin isolated from Glycine max (Soybean). Effect of SBL on intracellular mycobacterial viability through autophagy and the mechanism involved in differentiated THP-1 cells was studied using different experimental approaches.

NSC 18725, a Pyrazole Derivative Inhibits Growth of Intracellular by Induction of Autophagy.

The increasing incident rates of drug-resistant tuberculosis (DR-TB) is a global health concern and has been further complicated by the emergence of extensive and total drug-resistant strains. Identification of new chemical entities which are compatible with first-line TB drugs, possess activity against DR-, and metabolically less active bacteria is required to tackle this epidemic. Here, we have performed phenotypic screening of a small molecule library against BCG and identified 24 scaffolds that exhibited MIC values of at least 2.

Structure-function and application of plant lectins in disease biology and immunity.

Lectins are proteins with a high degree of stereospecificity to recognize various sugar structures and form reversible linkages upon interaction with glyco-conjugate complexes. These are abundantly found in plants, animals and many other species and are known to agglutinate various blood groups of erythrocytes. Further, due to the unique carbohydrate recognition property, lectins have been extensively used in many biological functions that make use of protein-carbohydrate recognition like detection, isolation and characterization of glycoconjugates, histochemistry of cells and tissues, tumor cell recognition and many more.

NU-6027 Inhibits Growth of Mycobacterium tuberculosis by Targeting Protein Kinase D and Protein Kinase G.

Tuberculosis (TB) is a global health concern, and this situation has further worsened due to the emergence of drug-resistant strains and the failure of BCG vaccine to impart protection. There is an imperative need to develop highly sensitive, specific diagnostic tools, novel therapeutics, and vaccines for the eradication of TB. In the present study, a chemical screen of a pharmacologically active compound library was performed to identify antimycobacterial compounds.

ESAT-6 modulates Calcimycin-induced autophagy through microRNA-30a in mycobacteria infected macrophages.

Objective: Mycobacterium tuberculosis (M. tb) has a sumptuous repertoire of effector molecules to counter host defenses. Some of these antigens inhibit autophagy but the exact mechanism of this inhibition is poorly understood.

Calcimycin induced IL-12 production inhibits intracellular mycobacterial growth by enhancing autophagy.

Previously, we reported pivotal role of P2RX7 in augmenting autophagy in THP-1 cells upon Calcimycin treatment by modulating intracellular Calcium regulated ATP production but the role of immune modulators in Calcimycin induced autophagy is not known. In this study, we demonstrate that treatment with Calcimycin in PMA (Phorbol 12-myristate 13-acetate) differentiated THP-1 (dTHP-1) cells significantly induced interleukin (IL)-12 mRNA expression and its release. IL-12 receptor (IL-12Rβ1 and IL-12Rβ2) was also significantly expressed on the cell surface in dTHP-1 cells upon Calcimycin treatment.

Calcimycin mediates mycobacterial killing by inducing intracellular calcium-regulated autophagy in a P2RX7 dependent manner.

Phenotypic screening led to the identification of calcimycin as a potent inhibitor of Mycobacterium bovis BCG (M. bovis BCG) growth in vitro and in THP-1 cells. In the present study, we aim to decipher the mechanism of antimycobacterial activity of calcimycin.