A5091669686- Antifungal resistance and susceptibility
- Pneumocystis jirovecii pneumonia detection and treatment
- Asthma and respiratory diseases
- Fungal Infections and Studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Pediatric health and respiratory diseases
- Occupational and environmental lung diseases
- Pneumonia and Respiratory Infections
- Neonatal Respiratory Health Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Immune Response and Inflammation
- Studies on Chitinases and Chitosanases
- Immunodeficiency and Autoimmune Disorders
- Tuberculosis Research and Epidemiology
- Reproductive tract infections research
- IL-33, ST2, and ILC Pathways
- Cystic Fibrosis Research Advances
- Respiratory viral infections research
- Psoriasis: Treatment and Pathogenesis
- Respiratory and Cough-Related Research
- Peptidase Inhibition and Analysis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Occupational exposure and asthma
- Antimicrobial Peptides and Activities
- Cytokine Signaling Pathways and Interactions
Tulane University
2018-2024
Tula University
2019
University of Alabama at Birmingham
2009-2018
Wake Forest University
2017
Pulmonary and Allergy Associates
2017
Queen Mary University of London
2014
University of Alabama
2012
University of Vermont
2008-2011
St. Vincent's Birmingham
2011
Children's Hospital of Pittsburgh
2004-2008
The inhalation of airborne pollutants, such as asbestos or silica, is linked to inflammation the lung, fibrosis, and lung cancer. How presence pathogenic dust recognized how chronic inflammatory diseases are triggered poorly understood. Here, we show that silica sensed by Nalp3 inflammasome, whose subsequent activation leads interleukin-1β secretion. Inflammasome reactive oxygen species, which generated a NADPH oxidase upon particle phagocytosis. (NADPH reduced form nicotinamide adenine...
Alveolar macrophages represent a first-line innate host defense mechanism for clearing inhaled Aspergillus fumigatus from the lungs, yet contradictory data exist as to which alveolar macrophage recognition receptor is critical immunity A. fumigatus. Acknowledging that cell wall contains high beta-1,3–glucan content, we questioned whether beta-glucan dectin-1 played role in this process. Monoclonal antibody, soluble receptor, and competitive carbohydrate blockage indicated inflammatory...
Immune suppression increases the incidence of invasive fungal infections, particularly those caused by opportunistic mold Aspergillus fumigatus. Previous investigations revealed that members TLR family are not absolutely required for host defense against A. fumigatus in nonimmunosuppressed hosts, suggesting other pattern recognition receptors involved. We show this study naive mice (i.e., pharmacologically immunosuppressed) lacking beta-glucan receptor Dectin-1 (Dectin-1(-/-)) more sensitive...
IL-17R signaling is critical for pulmonary neutrophil recruitment and host defense against Gram-negative bacteria through the coordinated release of G-CSF CXC chemokine elaboration. In this study, we show that localized to basal airway cells in human lung tissue, functional occurs on basolateral surface bronchial epithelial (HBE) cells. IL-17A IL-17F were potent inducers growth-related oncogene-alpha HBE cells, significant synergism was observed with TNF-alpha largely due via TNFRI. The...
Chronic inflammation involving both innate and adaptive immune cells is implicated in the pathogenesis of asthma. Intercellular communication essential for driving resolving inflammatory responses Emerging studies suggest that extracellular vesicles (EVs) including exosomes facilitate this process. In report, we have used a range approaches to show EVs contain markers mitochondria derived from donor which are capable sustaining membrane potential. Further, propose these participate...
Innate immune mechanisms against Pneumocystis carinii, a frequent cause of pneumonia in immunocompromised individuals, are not well understood. Using both real time polymerase chain reaction as measure organism viability and fluorescent deconvolution microscopy, we show that nonopsonic phagocytosis P. carinii by alveolar macrophages is mediated the Dectin-1 β-glucan receptor subsequent generation hydrogen peroxide involved macrophage–mediated killing carinii. The macrophage colocalized with...
ABSTRACT Vulvovaginal candidiasis (VVC) is an opportunistic mucosal infection caused by Candida albicans that affects large numbers of otherwise healthy women childbearing age. Acute episodes VVC often occur during pregnancy and the luteal phase menstrual cycle, when levels progesterone estrogen are elevated. Although estrogen-dependent experimental rodent models C. vaginal used for many applications, role reproductive hormones and/or their limits in acquisition remain unclear. This study...
Background Although the etiology of idiopathic pulmonary fibrosis (IPF) remains perplexing, adaptive immune activation is evident among many afflicted patients. Repeated cycles antigen-induced proliferation cause T-cells to lose surface expression CD28, and we hypothesized this process might also occur in IPF. Methodology/Principal Findings Peripheral blood CD4 from 89 IPF patients were analyzed by flow cytometry cytokine multiplex assays, correlated with clinical events. In comparison...
We evaluated cell-mediated immune (CMI) responses in mice given a pulmonary infection with Cryptococcus neoformans strain engineered to produce the Th1-type cytokine gamma interferon (IFN-gamma). Mice an IFN-gamma-producing C. were able resolve primary and demonstrated complete (100%) protection against second challenge pathogenic strain. Pulmonary analyses showed that Th1-type/proinflammatory chemokine expression significantly higher Th2-type was lower infected compared wild-type-infected...
Bone marrow-derived mesenchymal stromal cells (BMSCs) mitigate inflammation in mouse models of acute lung injury. However, specific mechanisms BMSC actions on CD4 T lymphocyte-mediated vivo remain poorly understood. Limited data suggests promotion Th2 phenotype Th1-mediated diseases. whether this might alleviate or worsen Th2-mediated diseases such as allergic asthma is unknown. To ascertain the effects systemic administration BMSCs a model airways inflammation, ovalbumin (OVA)-induced was...
We have previously reported that compromised interleukin 17A (IL-17A) production in the lungs increased susceptibility to infection with invasive fungal pathogen Aspergillus fumigatus. Here we shown culturing lung cells from A. fumigatus-challenged mice ex vivo demonstrated Dectin-1-dependent IL-17A production. In this system, neutralization of IL-23 but not IL-6, IL-1β, or IL-18 resulted attenuated Il23 mRNA expression was found be lower Dectin-1-deficient mice, whereas bone marrow-derived...
Allergic bronchopulmonary aspergillosis (ABPA) is caused by a dominant Th2 immune response to antigens derived from the opportunistic mold Aspergillus, most commonly Aspergillus fumigatus. It occurs in 4%-15% of patients with cystic fibrosis (CF); however, not all CF infected A. fumigatus develop ABPA. Therefore, we compared cohorts fumigatus-colonized and without ABPA identify factors mediating tolerance versus sensitization. We found that costimulatory molecule OX40 ligand (OX40L) was...
Reactive oxygen species are used by the immune system to eliminate infections; however, they may also serve as signaling intermediates coordinate efforts of innate and adaptive systems. In this study, we show that eliminating macrophage T cell superoxide production through NADPH oxidase (NOX), polarization was altered. After stimulation with immobilized anti-CD3 anti-CD28 or priming recall, cells from NOX-deficient mice exhibited a skewed Th17 phenotype, whereas NOX-intact produced cytokines...
We have previously reported that mice deficient in the beta-glucan receptor Dectin-1 displayed increased susceptibility to Aspergillus fumigatus lung infection presence of lower interleukin 23 (IL-23) and IL-17A production lungs a role for defense. As IL-23 is also thought control IL-22, we examined IL-22 production, as well innate host defense against A. fumigatus. Here, show Dectin-1-deficient demonstrated significantly reduced levels early after challenge. Culturing cells from enzymatic...
Sensitization to fungi, such as the mold Aspergillus fumigatus, is increasingly becoming linked with asthma severity. We have previously shown that lung responses generated via β-glucan receptor Dectin-1 are required for defense during acute, invasive A. fumigatus infection. Unexpectedly, in an allergic model of chronic exposure live conidia, recognition led induction multiple proallergic (Muc5ac, Clca3, CCL17, CCL22, and IL-33) proinflammatory (IL-1β CXCL1) mediators compromised function....
Abstract Background Pleural fibrosis and malignant mesotheliomas (MM) occur after exposures to pathogenic fibers, yet the mechanisms initiating these diseases are unclear. Results We document priming activation of NLRP3 inflammasome in human mesothelial cells by asbestos erionite that is causally related release IL-1β, IL-6, IL-8, Vascular Endothelial Growth Factor (VEGF). Transcription proteins inhibited vitro using Anakinra, an IL-1 receptor antagonist reduces cytokines a peritoneal MM...
Abstract Asthma is a chronic inflammatory disease process involving the conductive airways of human lung. The dysregulated response in this may involve multiple cell-cell interactions mediated by signaling molecules, including lipid mediators. Extracellular vesicles (EVs) are membrane particles that now recognized as critical mediators communication. Here, we compared composition and presence specific airway EVs purified from bronchoalveolar lavage (BAL) fluid healthy controls asthmatic...
ABSTRACT Oropharyngeal and vaginal candidiases are the most common forms of mucosal fungal infections primarily caused by Candida albicans , a dimorphic commensal organism gastrointestinal lower female reproductive tracts. Clinical experimental observations suggest that local immunity is important in host defense against candidiasis. Accordingly, cytokines chemokines present at oral mucosa during C. infections. Since epithelial cells produce variety response to microorganisms since closely...
Toll-like receptor 4 (TLR4) has been identified as a for lipopolysaccharide. However, the precise role of TLR4 in regulating gene expression response to an infection caused by gram-negative bacteria not fully elucidated. The signaling coordinating was assessed profiling lung tissue mouse model experimental pneumonia with low-dose Klebsiella pneumoniae. We analyzed four strains: C57BL/6 mice, which are resistant bacterial dissemination; 129/SvJ susceptible; C3H/HeJ susceptible and have...
Abstract CD4+CD25+FoxP3+ regulatory T cells are decreased in patients infected with HIV and have been shown to be critical mediating Ag tolerance the lung. Because a subset of Pneumocystis-infected individuals develop substantial lung injury, which can modeled immune reconstituted scid mice, we used mouse models Pneumocystis carinii investigate role opportunistic infection reconstitution. In this study, show that part host response CD4+ cell-intact mice. Moreover, injury proinflammatory Th1...
Lung neutrophilia is common to a variety of lung diseases. The production reactive oxygen and nitrogen species during neutrophil oxidative burst has been associated with protein DNA damage. Myeloperoxidase (MPO) an enzyme stored in the azurophilic granula neutrophils. It important host defense because it generates oxidant hypochlorous acid described play role activation neutrophils extravasation. We hypothesized that MPO contributes directly development acute via stimulation extravasation...
Cryptococcus neoformans is an opportunistic fungal pathogen that causes life-threatening pneumonia and meningoencephalitis in immune compromised individuals. Previous studies have shown immunization of BALB/c mice with IFN-gamma-producing C. strain, H99gamma, results complete protection against a second pulmonary challenge otherwise lethal cryptococcal strain. The current study evaluated local anamnestic cell-mediated responses cryptococcosis immunized strain H99gamma compared to heat-killed...
To determine relationship of echocardiographic measures pulmonary hypertension to lung function and inflammatory biomarkers in HIV-infected individuals.