- Inflammasome and immune disorders
- Vibrio bacteria research studies
- Legionella and Acanthamoeba research
- Cystic Fibrosis Research Advances
- Asthma and respiratory diseases
- Autophagy in Disease and Therapy
- Heme Oxygenase-1 and Carbon Monoxide
- Toxoplasma gondii Research Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Water Treatment and Disinfection
- Cell death mechanisms and regulation
- Immune Response and Inflammation
- Yersinia bacterium, plague, ectoparasites research
- Bacterial biofilms and quorum sensing
- Erythrocyte Function and Pathophysiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Allergic Rhinitis and Sensitization
- Biomedical Research and Pathophysiology
- Eicosanoids and Hypertension Pharmacology
- Alzheimer's disease research and treatments
- Kawasaki Disease and Coronary Complications
- Antibiotic Resistance in Bacteria
- Cerebrospinal fluid and hydrocephalus
- Phagocytosis and Immune Regulation
- Tryptophan and brain disorders
Birzeit University
2016-2023
The Ohio State University
2010-2022
The Ohio State University Wexner Medical Center
2019
Interface (United States)
2010-2013
Lung Institute
2012
University of Kentucky
2007-2010
Cystic fibrosis (CF) is the most common inherited lethal disease of Caucasians which results in multi organ dysfunction. However, 85% deaths are due to pulmonary infections. Infection by Burkholderia cenocepacia (B. cepacia) a particularly threat CF patients because it causes severe and persistent lung inflammation resistant nearly all available antibiotics. In CFTR ΔF508 mouse macrophages, B. cepacia persists vacuoles that do not fuse with lysosomes mediates increased production IL-1β. It...
Burkholderia cenocepacia is an opportunistic pathogen that causes chronic infection and induces progressive respiratory inflammation in cystic fibrosis patients. Recognition of bacteria by mononuclear cells generally results the activation caspase-1 processing IL-1β, a major proinflammatory cytokine. In this study, we report human pyrin required to detect intracellular B. leading IL-1β release. This inflammatory response involves host adapter molecule ASC bacterial type VI secretion system...
Gout is characterized by attacks of arthritis with hyperuricemia and monosodium urate (MSU) crystal-induced inflammation within joints. Innate immune responses are the primary drivers for tissue destruction in gout. MSU crystals engage Nlrp3 inflammasome leading to activation caspase-1 production IL-1β IL-18 gout-affected joints, promoting influx neutrophils monocytes. Here we show that caspase-11-/- mice their derived macrophages produce significantly reduced levels gout-specific cytokines...
Autophagy is a proposed route of amyloid-β (Aβ) clearance by microglia that halted in Alzheimer's Disease (AD), though mechanisms underlying this dysfunction remain elusive. Here, primary from adult AD (5xFAD) mice were utilized to demonstrate 5xFAD fail degrade Aβ and express low levels autophagy cargo receptor NBR1. In mouse brains, we show for the first time elevated microRNA cluster Mirc1/Mir17-92a, which known downregulate proteins. By situ hybridization post-mortem human tissue...
Cystic fibrosis is the most common inherited lethal disease in Caucasians. It caused by mutations cystic transmembrane conductance regulator (CFTR), of which cftr ΔF508 mutation common. macrophages are intrinsically defective autophagy because sequestration essential molecules within unprocessed CFTR aggregates. Defective allows Burkholderia cenocepacia (B. cepacia) to survive and replicate macrophages. Infection B. cepacia poses a great risk patients it causes accelerated lung inflammation...
The ability of Legionella pneumophila to cause pneumonia is determined by its capability evade the immune system and grow within human monocytes their derived macrophages. Human efficiently activate caspase-1 in response Salmonella but not L. pneumophila. molecular mechanism for lack inflammasome activation during infection unknown. Evaluation expression several components revealed that apoptosis-associated speck-like protein (ASC) NOD-like receptor NLRC4 are significantly down-regulated...
Legionella pneumophila (L. pneumophila) is an intracellular bacterium of human alveolar macrophages that causes Legionnaires' disease. In contrast to humans, most inbred mouse strains are restrictive L. replication. We demonstrate autophagy targets vacuoles lysosomes and this process requires ubiquitination the subsequent binding autophagic adaptor p62/SQSTM1 ubiquitinated vacuoles. The legA9 encodes for ankyrin-containing protein with unknown role. show mutant replicate in WT mice their...
Burkholderia cenocepacia (B. cenocepacia) is an opportunistic bacterium; causing severe life threatening systemic infections in immunocompromised individuals including cystic fibrosis patients. The lack of gasdermin D (GSDMD) protects mice against endotoxin lipopolysaccharide (LPS) shock. On the other hand, GSDMD promotes survival response to certain bacterial infections. However, role during B. infection not yet determined. Our vitro study shows that restricts replication within macrophages...
ABSTRACT Burkholderia cenocepacia infections in CF patients involve heightened inflammation, fatal sepsis, and high antibiotic resistance. Proinflammatory IL-1β secretion is important airway inflammation tissue damage. However, little known about this pathway macrophages upon B. infection. We report here that murine infected with K56-2 produce proinflammatory cytokine a TLR4 caspase-1-mediated manner. also determined the OPS (O antigen) of LPS contributes to production pyroptotic cell death....
The apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) is an adaptor molecule that mediates inflammatory and apoptotic signals. Legionella pneumophila intracellular bacterium the causative agent of Legionnaire's pneumonia. L. able to cause pneumonia in immuno-compromised humans but not most inbred mice. Murine macrophages lack ability activate caspase-1, such as caspase(-1-/-) Nlrc4(-/-) allow infection. This permissiveness attributed mainly active...
Legionella pneumophila, the causative agent of Legionnaire's disease, replicates in human alveolar macrophages to establish infection. There is no human-to-human transmission and main source infection L. pneumophila biofilms established air conditioners, water fountains, hospital equipments. The biofilm structure provides protection organism from disinfectants antibacterial agents. humans characterized by a subtle initial immune response, giving time for before patient succumbs pneumonia....
Article21 October 2019Open Access Transparent process Caspase-11 counteracts mitochondrial ROS-mediated clearance of Staphylococcus aureus in macrophages Kathrin Krause Department Microbial Infection and Immunity, Infectious Diseases Institute, Ohio State University, Columbus, OH, USA Search for more papers by this author Kylene Daily Shady Estfanous Kaitlin Hamilton Asmaa Badr Arwa Abu Khweek Biology Biochemistry, Birzeit Birzeit, West Bank, Palestine Rana Hegazi Midhun NK Anne Brett Klamer...
The Yersinia pestis Hms(+) phenotype is a manifestation of biofilm formation that causes adsorption Congo red and haemin at 26 degrees C but not 37 C. This required for blockage the proventricular valve oriental rat flea plays role in transmission bubonic plague from fleas to mammals. Genes responsible this are located three separate operons, hmsHFRS, hmsT hmsP. HmsH HmsF outer membrane (OM) proteins, while other four Hms proteins inner membrane. According Hidden Markov Method-based...
Cystic fibrosis (CF) human and mouse macrophages are defective in their ability to clear bacteria such as
L. pneumophila is the causative agent of Legionnaires' disease, a human illness characterized by severe pneumonia. In contrast to those derived from humans, macrophages most mouse strains restrict replication. The restriction replication has been shown require bacterial flagellin, component type IV secretion system as well cytosolic NOD-like receptor (NLR) Nlrc4/ Ipaf. These events lead caspase-1 activation which, in turn, activates caspase-7. Following caspase-7 activation,...
Legionella pneumophila is the causative agent of Legionnaires' disease, a serious and often fatal form pneumonia. The susceptibility to L. arises from ability this intracellular pathogen multiply in human alveolar macrophages monocytes. also replicates several professional non-professional phagocytic human-derived cell lines. With exception A/J mouse strain, most mice strains are restrictive, thus they do not support replication. Mice lacking NOD-like receptor Nlrc4 or caspase-1 susceptible...
BackgroundMitochondria play a key role in immune defense pathways, particularly for macrophages. We and others have previously demonstrated that cystic fibrosis (CF) macrophages exhibit weak autophagy activity exacerbated inflammatory responses. Previous studies revealed mitochondria are defective CF epithelial cells, but to date, the connection between mitochondrial function macrophage dysregulation has not been fully elucidated. Here, we present characterization of dysfunction...
Legionella pneumophila, a causative agent of Legionnaire's disease, replicates in human alveolar macrophages and establish infection humans. There is no to transmission the main source L. pneumophila biofilms established air conditioners water fountains. Biofilm structure provides protection for organism from disinfectants antibacterial agents. humans characterized by subtle initial immune response giving time before patient succumbs pneumonia. Planktonic elicits strong murine but not...