A5066189835- Fungal Infections and Studies
- Antifungal resistance and susceptibility
- Studies on Chitinases and Chitosanases
- Polysaccharides and Plant Cell Walls
- Immunotherapy and Immune Responses
- Carbohydrate Chemistry and Synthesis
- Autophagy in Disease and Therapy
- Plant-Microbe Interactions and Immunity
- Asthma and respiratory diseases
- Medicinal Plant Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Bacterial biofilms and quorum sensing
- Pediatric health and respiratory diseases
- Phytochemistry and Biological Activities
- Biological Research and Disease Studies
- Immune Response and Inflammation
- Antimicrobial Peptides and Activities
- Antimicrobial Resistance in Staphylococcus
- Glycosylation and Glycoproteins Research
- Microbial Metabolites in Food Biotechnology
- Bacterial Genetics and Biotechnology
- Fungal and yeast genetics research
- Metabolism, Diabetes, and Cancer
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
Massachusetts General Hospital
2010-2020
Harvard University
2011-2020
University of Massachusetts Chan Medical School
2018-2019
University of Massachusetts Lowell
2016-2019
Office of Infectious Diseases
2013-2014
In-Q-Tel
2011
Autophagy has been postulated to play role in mammalian host defense against fungal pathogens, although the molecular details remain unclear. Here, we show that primary macrophages deficient autophagic factor LC3 demonstrate diminished fungicidal activity but increased cytokine production response Candida albicans stimulation. recruitment phagosomes requires activation of pattern receptor dectin-1. phagosome also Syk signaling is independent all by Toll-like receptors and does not require...
Elimination of fungal pathogens by phagocytes requires phagosome maturation, a process that involves the recruitment and fusion intracellular proteins. The role Dectin-1, β-1,3-glucan receptor, critical for recognition triggering Th17 responses, to phagosomal maturation has not been defined. We show GFP-Dectin-1 translocates phagosome, but its signal decays after 2 h. Inhibition acidification results in retention membranes highlighting requirement an acidic pH. Following recognition,...
Phagocytic responses are critical for effective host defense against opportunistic fungal pathogens. Macrophages sample the phagosomal content and orchestrate innate immune response. Toll-like receptor 9 (TLR9) recognizes unmethylated CpG DNA is activated by DNA. Here we demonstrate that specific triggering of TLR9 recruitment to macrophage membrane a conserved feature fungi distinct phylogenetic origins, including Candida albicans, Saccharomyces cerevisiae, Malassezia furfur, Cryptococcus...
Abstract Dectin-1 and TLR9 play distinct roles in the recognition induction of innate immune responses to Aspergillus fumigatus Candida albicans. is a receptor for major fungal cell wall carbohydrate β-1,3 glucan that induces inflammatory cytokines controls phagosomal maturation through spleen tyrosine kinase activation. an endosomal TLR also modulates cytokine response pathogens. In this study, we demonstrate beads are sufficient induce dynamic redistribution accumulation cleaved...
Neutrophils are recognized to represent significant immune cell mediators for the clearance and elimination of human-pathogenic fungal pathogen Candida . The sensing fungi by innate cells is performed, in part, through lectin receptor recognition wall components downstream cellular activation signaling components, including spleen tyrosine kinase (Syk). While essential role Syk macrophages dendritic clear, there remains uncertainty with respect its contribution neutrophils. In this study, we...
Tetraspanins are a family of proteins possessing four transmembrane domains that help in lateral organization plasma membrane proteins. These interact with each other as well receptors and signaling proteins, resulting functional complexes called "tetraspanin microdomains." Tetraspanins, including CD82, play an essential role the pathogenesis fungal infections. Dectin-1, receptor for cell wall carbohydrate β-1,3-glucan, is vital to host defense against The current study identifies novel...
Journal Article Use of fungal derived polysaccharide-conjugated particles to probe Dectin-1 responses in innate immunity Get access Jenny M. Tam, Tam Department Medicine, Division Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, GRJ-5-504, Boston, MA 02114, USA. Fax: +1 617 643 6443; Tel: 6444 Search for other works by this author on: Oxford Academic Google Scholar Michael K. Mansour, Mansour Nida S. Khan, Khan Nicholas C. Yoder, Yoder Whitehead...
ABSTRACT CD82 is a member of the tetraspanin superfamily, whose physiological role best described in context cancer metastasis. However, also associates with components class II major histocompatibility complex (MHC) antigen presentation pathway, including MHC molecules and peptide-loading machinery, as well CD63, another tetraspanin, suggesting for presentation. Here, we observe dynamic rearrangement after pathogen uptake by imaging CD82-mRFP1 expressed primary living dendritic cells....
ABSTRACT We previously reported that the Tet38 efflux pump is involved in internalization of Staphylococcus aureus by A549 lung epithelial cells. A lack tet38 reduced bacterial uptake cells to 36% parental strain RN6390. Using invasion assays coupled with confocal microscopy imaging, we studied host cell receptor(s) responsible for via interaction Tet38. also assessed ability S. survive following alkalinization phagolysosomes chloroquine. Antibody scavenger receptor CD36 RN6390 cells, but...
The tetraspanin CD82 is a potent suppressor of tumor metastasis and regulates several processes including signal transduction, cell adhesion, motility, aggregation. However, the mechanisms by which participates in innate immunity are unknown. We report that key regulator TLR9 trafficking signaling. recognizes unmethylated cytosine-phosphate-guanine (CpG) motifs present viral, bacterial, fungal DNA. demonstrate associate macrophages, occurs endoplasmic reticulum (ER) post-ER. Moreover,...
Candida spp. are the fourth leading cause of nosocomial blood stream infections in North America. glabrata is second most frequently isolated species, and rapid development antifungal resistance has made treatment a challenge. In this study, we investigate therapeutic potential metformin, biguanide with well-established action for diabetes, as an agent against C. glabrata. Both wild type antifungal-resistant isolates were subjected to biguanide-antifungal combination treatment. Metformin,...
Macrophages play a critical role in the elimination of fungal pathogens. They are sensed via cell surface pattern-recognition receptors and phagocytosed into newly formed organelles called phagosomes. Phagosomes mature through recruitment proteins lysosomes, resulting addition proteolytic enzymes acidification microenvironment. Our earlier studies demonstrated an essential Dectin-1-dependent activation spleen tyrosine kinase (Syk) maturation containing The absence Syk activity interrupted...
Dematiaceous molds are found ubiquitously in the environment and cause a wide spectrum of human disease, including infections associated with high rates mortality. Despite this, mechanism innate immune response has been less well studied, although it is key clearance fungal pathogens. Here, we focus on Exserohilum rostratum, dematiaceous mold that caused 753 during multistate outbreak due to injection contaminated methylprednisolone. We show macrophages incapable phagocytosing lack...
Abstract Dectin-1 recognizes the fungal wall carbohydrate, β-1,3-D-glucan. Defects in have been isolated patients suffering from recurrent Candidal infections demonstrating essential role of carbohydrate recognition eliciting protective immunity. In following work, we sought to characterize intracellular steps β-1,3-D-glucan phagocytosis by macrophages. previous studies, described a fungal-like particle (FLP) consisting polystyrene bead platform covalently conjugated thus mimicking geometry...
Abstract A classic hallmark in the autophagic process is reversible conjugation of LC3 to autophagosomal membrane. Autophagy has been shown target pathogens that reside cytosol or within autophagosomes for lysosomal degradation. Therefore, components autophagy pathway can participate effective elimination viruses, bacteria, and parasites, though their role fungal immunity poorly understood. We show activation Dectin-1 by its ligand β-1,3-glucan leads recruitment phagosome describe multiple...
Abstract The presence of multiple types carbohydrate moieties on fungal cell walls prohibits elucidation the exact immunological response to pathogen-derived epitopes. To dissect mechanisms used recognize pathogens, a system “fungal like particles” was developed that consisted polymer beads, which mimicked three dimensional shape fungus, coated covalently with purified b-1,3-glucan (BG) derived from S. cerevisiae. morphology BG layer examined by immunofluorescence, flow cytometery, and...