A5072803795- Leprosy Research and Treatment
- Mycobacterium research and diagnosis
- Pharmacological Effects of Natural Compounds
- Tuberculosis Research and Epidemiology
- Peripheral Neuropathies and Disorders
- Infectious Diseases and Tuberculosis
- Herpesvirus Infections and Treatments
- Toxin Mechanisms and Immunotoxins
- Heat shock proteins research
- Bacterial Genetics and Biotechnology
- Hepatitis B Virus Studies
- Escherichia coli research studies
- Immunotherapy and Immune Responses
- Chronic Lymphocytic Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- T-cell and B-cell Immunology
- Bacteriophages and microbial interactions
- CRISPR and Genetic Engineering
- Allergic Rhinitis and Sensitization
- Skin and Cellular Biology Research
- Coccidia and coccidiosis research
- Immunotoxicology and immune responses
- Childhood Cancer Survivors' Quality of Life
- Autoimmune and Inflammatory Disorders
University of Edinburgh
2009-2022
MRC Centre for Regenerative Medicine
2011-2022
Medical Research Council
2019-2020
Rockefeller University
2000-2013
National Center for Infectious Diseases
2013
University of Iowa
1998-2003
Howard Hughes Medical Institute
1998-2003
Scripps Research Institute
2003
American Association For The Advancement of Science
2002
Teikyo University
1999
SummaryDifferentiated cells possess a remarkable genomic plasticity that can be manipulated to reverse or change developmental commitments. Here, we show the leprosy bacterium hijacks this property reprogram adult Schwann cells, its preferred host niche, stage of progenitor/stem-like (pSLC) mesenchymal trait by downregulating cell lineage/differentiation-associated genes and upregulating mostly mesoderm development. Reprogramming accompanies epigenetic changes renders infected highly...
alpha-Dystroglycan (alpha-DG) is a component of the dystroglycan complex, which involved in early development and morphogenesis pathogenesis muscular dystrophies. Here, alpha-DG was shown to serve as Schwann cell receptor for Mycobacterium leprae, causative organism leprosy. leprae specifically bound only presence G domain alpha2 chain laminin-2. Native competitively inhibited laminin-2-mediated M. binding primary cells. Thus, may use linkage between extracellular matrix cytoskeleton through...
Demyelination results in severe disability many neurodegenerative diseases and nervous system infections, it is typically mediated by inflammatory responses. Mycobacterium leprae , the causative organism of leprosy, induced rapid demyelination a contact-dependent mechanism absence immune cells an vitro nerve tissue culture model Rag1 -knockout ( −/− ) mice, which lack mature B T lymphocytes. Myelinated Schwann were resistant to M. invasion but undergo upon bacterial attachment, whereas...
We report that the molecular basis of neural tropism Mycobacterium leprae is attributable to specific binding M. laminin-α2 (LN-α2) chain on Schwann cell–axon units. Using recombinant fragments LN-α2 (rLN-α2), leprae-binding site was localized G domain. rLN-α2G mediated cell lines and sciatic nerves dystrophic dy/dy mice lacking LN-α2, but expressing laminin receptors. Anti-β4 integrin antibody attenuated rLN-α2G-mediated adherence, suggesting interacts with cells by β4 via an LN-α2G bridge....
Nerve damage is a clinical hallmark of leprosy and major source patient morbidity. We investigated the possibility that human Schwann cells are susceptible to cell death through activation Toll-like receptor 2 (TLR2), pattern recognition innate immune system. TLR2 was detected on surface line ST88-14 cultured primary cells. Activation cultures with agonist, synthetic lipopeptide comprising N-terminal portion putative Mycobacterium leprae 19-kDa lipoprotein, triggered an increase in number...
Nerve damage is the hallmark of Mycobacterium leprae infection, which results from M. invasion Schwann cell peripheral nervous system. We have recently shown that laminin-2 isoform, specially G domain laminin α2 chain, on cell–axon unit serves as an initial neural target for . However, surface molecules mediate bacterial nerves are entirely unknown. By using human laminins a probe, major 28-kDa protein in wall fraction binds was identified. After N-terminal amino acid sequence analysis,...
Activation of extracellular signal-regulated kinase (Erk) 1/2, which plays a critical role in diverse cellular processes, including cell proliferation, is known to be mediated by the canonical Raf-mitogen-activated protein (MEK) cascade. Alternative MEK-independent signaling pathways for Erk1/2 activation mammalian cells are not known. During our studies human primary Schwann response long-term infection Mycobacterium leprae , causative organism leprosy, we identified that intracellular M....
Recently, we showed a natural reprogramming process during infection with Mycobacterium leprae (ML), the causative organism of human leprosy. ML hijacks notable plasticity adult Schwann cells in peripheral nervous system (PNS), bacteria's preferred nonimmune niche, to reprogram infected progenitor/stem cell-like (pSLCs). Whereas appear use this as sophisticated bacterial strategy spread other tissues, understanding mechanisms may shed new insights into basic biology cellular and development...
Iron is an essential metal for living organisms but its level must be strictly controlled in cells, because ferrous ion induces toxicity by generating highly active reactive oxygen, hydroxyl radicals, through the Fenton reaction. In addition, ferric shows low solubility under physiological conditions. To overcome these obstacles possess Ferritin superfamily proteins that are distributed all three domains of life: bacteria, archaea, and eukaryotes. These minimize radical formation ferroxidase...
Abstract CD1d-restricted NKT cells expressing invariant TCR α-chains (iNKT cells) produce both proinflammatory and anti-inflammatory cytokines rapidly upon activation, are believed to play an important role in host defense immunoregulation. To address the potential implications of iNKT cell responses for infectious or inflammatory diseases nervous system, we investigated expression CD1d human peripheral nerve. We found that was expressed on surface Schwann situ primary immortalized lines...
Two different groups of monoclonal antibodies (MAbs) directed to epitopes on 30‐kDa region proteins Mycobacterium tuberculosis were isolated; MAbs 5F9, 5D5 and 5D2 reacted with a single 33‐kDa protein band, whereas MAb 3A8 readied A distinct 29,33‐kDa doublet when analysed by immunoblotting. The present paper describes the distribution defined in 29 well‐characterized subcellular fractions: cytosol, plasma membrane, cell wall as well culture filtrate M. tuberculosis. reactive found 3AS...
Immunoblot assays for the antibodies to Mycobacterium tuberculosis sonic extracts showed that all serum specimens of 40 lepromatous and 28 tuberculoid leprosy patients reacted in a significant manner 29/33-kilodalton (kDa) doublet 64-kDa antigens, respectively. By using an enzyme-linked immunosorbent assay, we observed significantly high immunoglobulin G antibody titer purified M. 29/33-kDa antigens patients, respectively, as compared with normal subjects patients. This assay serology may be...
Ideal therapies for regenerative medicine or healthy aging require organ growth and rejuvenation, but no organ-level approach is currently available. Using Mycobacterium leprae (ML) with natural partial cellular reprogramming capacity its animal host nine-banded armadillos, we present an evolutionarily refined model of adult liver regeneration. In infected ML reprogram the entire significantly increase total liver/body weight ratio by increasing lobules, including hepatocyte proliferation...