A5081958428- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Antimicrobial Peptides and Activities
- Immune Cell Function and Interaction
- Immune cells in cancer
- Toxoplasma gondii Research Studies
- Neonatal Respiratory Health Research
- Influenza Virus Research Studies
- Escherichia coli research studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Bacterial Infections and Vaccines
- Gut microbiota and health
- T-cell and B-cell Immunology
- Heat shock proteins research
- Cytomegalovirus and herpesvirus research
- Herpesvirus Infections and Treatments
- Cellular Mechanics and Interactions
- RNA Interference and Gene Delivery
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- IL-33, ST2, and ILC Pathways
- CAR-T cell therapy research
- Wound Healing and Treatments
- Adipokines, Inflammation, and Metabolic Diseases
- Cell Adhesion Molecules Research
Cornell University
2014-2024
New York State College of Veterinary Medicine
2006-2018
National Institutes of Health
2003-2006
National Cancer Institute
2002-2005
Center for Biologics Evaluation and Research
2001-2003
National Institute of Diabetes and Digestive and Kidney Diseases
2003
Temple University
1980
University of Pennsylvania
1980
beta-Defensins are small antimicrobial peptides of the innate immune system produced in response to microbial infection mucosal tissue and skin. We demonstrate that murine beta-defensin 2 (mDF2beta) acts directly on immature dendritic cells as an endogenous ligand for Toll-like receptor 4 (TLR-4), inducing up-regulation costimulatory molecules cell maturation. These events, turn, trigger robust, type 1 polarized adaptive responses vivo, suggesting mDF2beta may play important role...
To investigate the role of Toll-like receptor (TLR)9 in immune response to mycobacteria as well its cooperation with TLR2, a known be triggered by several major mycobacterial ligands, we analyzed resistance TLR9−/− TLR2/9 double knockout mice aerosol infection Mycobacterium tuberculosis. Infected but not TLR2−/− displayed defective mycobacteria-induced interleukin (IL)-12p40 and interferon (IFN)-γ responses vivo, common animals, exhibited only minor reductions acute low dose pathogen...
Unmethylated CpG motifs present in bacterial DNA stimulate a rapid and robust innate immune response. Human cell lines PBMC that recognize express membrane-bound human Toll-like receptor 9 (hTLR9). Cells are not responsive to become when transfected with hTLR9. Expression of hTLR9 dramatically increases uptake (but control) into endocytic vesicles. Upon stimulation, found the same expressing stimulated by active primates but rodents, suggesting evolutionary divergence between TLR9 molecules...
Virtually all of the elements Mycobacterium tuberculosis (Mtb) pathogenesis, including pro-inflammatory cytokine production, granuloma formation, cachexia, and mortality, can be induced by its predominant cell wall glycolipid, trehalose 6,6′-dimycolate (TDM/cord factor). TDM mediates these potent inflammatory responses via interactions with macrophages both in vitro vivo a myeloid differentiation factor 88 (MyD88)-dependent manner phosphorylation mitogen activated protein kinases (MAPKs),...
In mammals, 10 TLRs recognize conserved pathogen-associated molecular patterns, resulting in the induction of inflammatory innate immune responses. One these, TLR9, is activated intracellularly by bacterial DNA and synthetic oligodeoxynucleotides (ODN), containing unmethylated CpG dinucleotides. Following treatment with ODN, TLR9 found lysosome-associated membrane protein type 1-positive lysosomes, we asked which intracellular compartment contains before exposure. Surprisingly, microscopy...
Abstract The cytokines secreted by pathogen-activated human dendritic cells (DC) are strongly regulated in vitro histamine, a major component of mast cell granules, ultimately modulating the capacity DC to polarize naive T cells. Because and located close proximity peripheral compartments, we hypothesized that products would influence maturation hence Th balance an immune response vivo. In this study, show specific degranulation stimuli, given s.c. mice with Ag adjuvant, produce effector...
Toll‐like receptor 9 (TLR9) promiscuously binds self‐ and microbial DNA, but only DNA elicits an inflammatory response. How TLR9 discriminates between foreign is unclear, inappropriate localization of permits response to self‐DNA, suggesting that trafficking are critical components. The molecular mechanisms controlling the movement may provide new insight into recognition in normal pathological conditions such as autoimmune systemic lupus erythematosus. We have shown earlier retained...
Toll-like receptors (TLRs) are innate critical for host defense and play a role in normal biological processes. For example, DNA, TLR9 ligand, stimulates epithelial repair following skin wounding. TLR signaling also plays crucial regulating intestinal homeostasis. We therefore asked whether is important wound using dextran sulfate sodium (DSS)-induced damage model. showed that TLR9-deficient mice more susceptible to DSS exhibited delayed at both the clinical histologic levels. reduced gene...
Advanced cancer causes necrosis and releases damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs activate neutrophils, including generation of neutrophil extracellular traps (NETs), which are injurious, thrombogenic, implicated in metastasis. We hypothesised that mitochondrial DNA (mtDNA) ascites from patients with epithelial ovarian (EOC) would correlate worse outcomes.Banked supernatants newly diagnosed advanced EOC were analysed for mtDNA, elastase, activation healthy donor...
All biomaterials, including biologic scaffolds composed of extracellular matrix (ECM), elicit a host immune response when implanted. The type and intensity this depends in part upon the thoroughness decellularization removal cell debris from source tissue. Proinflammatory responses have been associated with negative downstream remodeling events scar tissue formation, encapsulation, seroma formation. relative effects specific cellular components inflammatory are not known. objective present...
Abstract Macrophages participate in immunity, tissue repair and homeostasis. Activation of Toll-like receptors (TLRs) by conserved exogenous or endogenous structures initiates signaling cascades that result the release cytokines such as tumor necrosis factor α (TNFα). Extracellular substrate stiffness is known to regulate functions non-immune cells through a process called mechanotransduction, yet less about how physical cues affect macrophage function TLR signaling. To investigate this...
MD-2, a glycoprotein that is essential for the innate response to lipopolysaccharide (LPS), binds both LPS and extracellular domain of Toll-like receptor 4 (TLR4). Following synthesis, MD-2 either secreted directly into medium as soluble, active protein, or TLR4 in endoplasmic reticulum before migrating cell surface. Here we investigate function form MD-2. We show irreversibly loses activity over 24-h period at physiological temperature. LPS, but not lipid A, prevents this loss by forming...
Toll-like receptors (TLRs) are essential for host defense. Although several TLRs reside on the cell surface, nucleic acid recognition of occurs intracellularly. For example, receptor CpG containing bacterial and viral DNA, TLR9, is retained in endoplasmic reticulum. Recent evidence suggests that localization TLR9 critical appropriate ligand recognition. Here we have defined which structural features molecule control its intracellular localization. Both cytoplasmic ectodomains contain...
Polymorphonuclear leukocytes (PMNs) come in contact with plaque microorganisms the gingival sulcus. However, little is known about ability of PMNs to kill or inhibit growth microorganisms. In this study, bactericidal effects human and serum against S. mutans 6715, sanguis M5, A. viscosus T14 virulent avirulent were examined. Plaque grown stationary phase incubated and/or for 90 minutes at 37°C. The killing inhibition bacteria determined by measurement percent reduction colony forming units...
Grp94 is involved in the regulation of a restricted number proteins and represents potential target host diseases, including cancer, septic shock, autoimmune chronic inflammatory conditions, diabetes, coronary thrombosis, stroke. We have recently identified novel allosteric pocket located N-terminal binding site that can be used to design ligands with 2-log selectivity over other Hsp90 paralogs. Here we perform extensive SAR investigations this ligand series rationalize affinity paralog...
Plasmacytoid dendritic cells (DC) are professional APC and a major source of type I IFN following viral infection. We previously showed that histamine alters the cytokine profiles maturing monocyte-derived DC resulting in change from Th1 to Th2 their T cell polarizing function. In this study, we show human plasmacytoid DC, activated by either CpG oligodeoxynucleotides or infection, also respond through H2 receptors, leading marked down-regulation IFN-alpha TNF-alpha moderate switch capacity...
Abstract Background Inflammatory bowel diseases (IBDs) are chronic, relapsing disorders that affect the gastrointestinal tract of millions people and continue to increase in incidence each year. While several factors have been associated with development IBDs, exact etiology is unknown. Research using animal models IBDs beginning provide insights into how different contribute disease development. Oral administration dextran sulfate sodium (DSS) mice induces a reproducible experimental...
Recombinant subunit vaccine engineering increasingly focuses on the development of more effective delivery platforms. However, current recombinant vaccines fail to sufficiently stimulate protective adaptive immunity against a wide range pathogens while remaining cost solution global health challenges. Taking an unorthodox approach this fundamental immunological challenge, we isolated TLR-targeting capability probiotic E. coli Nissle 1917 bacteria (EcN) by bionanoparticlate antigen carriers...