<p>Either PMA stimulated THP1 macrophages (Panel A and B) or blood monocyte derived macrophages (Panel C and D) were treated with inhibitor to either calcium influx from external medium (EGTA; thin lines) or calcium influx from... more
<p>Either PMA stimulated THP1 macrophages (Panel A and B) or blood monocyte derived macrophages (Panel C and D) were treated with inhibitor to either calcium influx from external medium (EGTA; thin lines) or calcium influx from internal stores (TMB-8; thick lines) for 1h and stimulated with 1 μg/ml Pam3CSK4 along with 20 μg/ml Rv3416 and 15 μg/ml Nef for 24h. At the end of the incubation period cells were stained with Annexin V-APC. Shaded histograms in Panel A and Panel C represent cells stimulated with 1 μg/ml Pam3CSK4 along with 20 μg/ml Rv3416 and 15 μg/ml Nef for 24h. Bar graphs adjacent to histograms in Panel A and Panel C show relative MFIs of the histograms. Data from one of three independent experiments are shown. For Panel B (THP-1 macrophages) and Panel D (blood macrophages) were treated as indicated for 24h. Cytoplasmic extracts were probed for indicated molecules and analyzed by western blots. Numbers below the blots indicate the relative intensities of the bands. Data from one of three experiments are shown. In Panel A, P<0.04 for Pam+Rv3416+Nef vs Pam+Rv3416+Nef+EGTA. P<0.01 for Pam+Rv3416+Nef vs Pam+Rv3416+Nef+TMB8. In Panel C, P<0.05 for Pam+Rv3416+Nef vs Pam+Rv3416+Nef+EGTA. P<0.03 for Pam+Rv3416+Nef vs Pam+Rv3416+Nef+TMB8.</p
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Pneumonia leads to high mortality in children under the age of five years worldwide, resulting in close to 20 percent of all deaths in this age group. Therefore, investigations into host-pathogen interactions during Streptococcus... more
Pneumonia leads to high mortality in children under the age of five years worldwide, resulting in close to 20 percent of all deaths in this age group. Therefore, investigations into host-pathogen interactions during Streptococcus pneumoniae infection are key in devising strategies towards the development of better vaccines and drugs. To that end, in this study we investigated the role of S. pneumoniae and its surface antigen Pneumococcal surface protein A (PspA) in modulating the expression of co-stimulatory molecule Programmed Death Ligand 1 (PD-L1) expression on dendritic cells (DCs) and the subsequent effects of increased PD-L1 on key defence responses. Our data indicate that stimulation of DCs with PspA increases the surface expression of PD-L1 in a time and dose dependent manner. Characterization of mechanisms involved in PspA induced expression of PD-L1 indicate the involvement of Toll-Like Receptor 2 (TLR2) and calcium homeostasis. While calcium release from intracellular sto...
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The emergence of drug resistant strains of Mycobacterium tuberculosis (M. tuberculosis) together with reports of co-infections with the human immunodeficiency virus (HIV) has renewed interest to better understand the intricate mechanisms... more
The emergence of drug resistant strains of Mycobacterium tuberculosis (M. tuberculosis) together with reports of co-infections with the human immunodeficiency virus (HIV) has renewed interest to better understand the intricate mechanisms prevalent during co-infections. In this study we report a synergistic effect of M. tuberculosis and HIV-1, and their antigens Rv3416 and Nef, respectively, in inhibiting apoptosis of macrophages. This inhibition involves the TLR2 pathway and second messengers that play complementing and contrasting roles in regulating apoptosis. Interestingly, the route of calcium influx into cells differentially regulates apoptosis during antigenic co-stimulation. While calcium released from intracellular stores was anti-apoptotic, calcium influx from the external milieu was pro-apoptotic. Further, molecular sensors of intracellular calcium release aid in antigen mediated inhibition of apoptosis. A cross-regulation between oxidative burst and differential routing o...
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Research Interests: Biology, Autophagy, Apoptosis, Medicine, Dendritic Cells, and 14 moreToll Like Receptors, RNA interference, Tuberculosis, Mycobacterium tuberculosis, Female, Animals, Calcium Signaling, Phagocytosis, Transfection, Host Pathogen Interactions, Respiratory Burst, Ubiquitination, Mitogen- Activated Protein Kinases, and Medical and Health Sciences
Research Interests: Biology, Calcium, Autophagy, Biological Chemistry, Dendritic Cells, and 14 moreBiological Sciences, Mycobacterium tuberculosis, Reactive Oxygen Species, Mice, Immunity, Female, Animals, Superoxide Dismutase, CHEMICAL SCIENCES, T lymphocytes, Calmodulin, Respiratory Burst, Cell Adhesion Molecules, and Medical and Health Sciences
Research Interests: Immunology, Immune response, Biology, Cytokines, Macrophages, and 14 moreMedicine, T cell receptor, Signal Transduction, Toll like receptor signaling, RNA interference, Tuberculosis, Mycobacterium tuberculosis, Mice, Female, Animals, Dendritic cell, Biochemistry and cell biology, Cell Adhesion Molecules, and Interleukin
Complement system is the first line of human defence against intruding pathogens and is recognized as a potentially useful therapeutic target. Human malaria parasite employs a series of intricate mechanisms that enables it to evade... more
Complement system is the first line of human defence against intruding pathogens and is recognized as a potentially useful therapeutic target. Human malaria parasite employs a series of intricate mechanisms that enables it to evade different arms of immune system, including the complement system. Here, we show the expression of a multi-domain Complement Control Protein 1, PfCCp1 at asexual blood stages and its binding affinity with C3b as well as C4b proteins of human complement cascade. Using a biochemical assay, we demonstrate that PfCCp1 binds with complement factors and inhibits complement activation. Active immunization of mice with PfCCp1 followed by challenge with resulted in the loss of biphasic growth of parasites and early death in comparison to the control group. The study also showed a role of PfCCp1 in modulating TLR mediated signalling and effector responses on antigen presenting cells. PfCCp1 binds with Dendritic cells that down-regulates the expression of signalling ...
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Pneumonia leads to high mortality in children under the age of five years worldwide, result-ing in close to 20 percent of all deaths in this age group. Therefore, investigations into host-pathogen interactions during Streptococcus... more
Pneumonia leads to high mortality in children under the age of five years worldwide, result-ing in close to 20 percent of all deaths in this age group. Therefore, investigations into host-pathogen interactions during Streptococcus pneumoniae infection are key in devising strat-egies towards the development of better vaccines and drugs. To that end, in this study we investigated the role of S. pneumoniae and its surface antigen Pneumococcal surface protein A (PspA) in modulating the expression of co-stimulatory molecule Programmed Death Ligand 1 (PD-L1) expression on dendritic cells (DCs) and the subsequent effects of increased PD-L1 on key defence responses. Our data indicate that stimulation of DCs with PspA increases the surface expression of PD-L1 in a time and dose dependent manner. Characterization of mechanisms involved in PspA induced expression of PD-L1 indicate the involvement of Toll-Like Receptor 2 (TLR2) and calcium homeostasis. While calcium release from intracellular s...
Resistance to therapy is the major hurdle in the current cancer management. Cancer cells often rewire their cellular process to alternate mechanisms to resist the deleterious effect mounted by different therapeutic approaches. The major... more
Resistance to therapy is the major hurdle in the current cancer management. Cancer cells often rewire their cellular process to alternate mechanisms to resist the deleterious effect mounted by different therapeutic approaches. The major signaling pathways involved in the developmental process, such as Notch, Hedgehog, and Wnt, play a vital role in development, tumorigenesis, and also in the resistance to the various anticancer therapies. Understanding how cancer utilizes these developmental pathways in acquiring the resistance to the multi-therapeutic approach cancer can give rise to a new insight of the anti-therapy resistance mechanisms, which can be explored for the development of a novel therapeutic approach. We present a brief overview of Notch, Hedgehog, and Wnt signaling pathways in cancer and its role in providing resistance to various cancer treatment modalities such as chemotherapy, radiotherapy, molecular targeted therapy, and immunotherapy. Understanding the importance o...