A5055750591- Immune Response and Inflammation
- Immune Cell Function and Interaction
- Influenza Virus Research Studies
- Respiratory viral infections research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- interferon and immune responses
- IL-33, ST2, and ILC Pathways
- Pregnancy and Medication Impact
- Arsenic contamination and mitigation
- NF-κB Signaling Pathways
- Eosinophilic Disorders and Syndromes
- Immunotherapy and Immune Responses
- Immunodeficiency and Autoimmune Disorders
- Immune cells in cancer
- Pediatric health and respiratory diseases
- Cytokine Signaling Pathways and Interactions
- Asthma and respiratory diseases
- T-cell and B-cell Immunology
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Antimicrobial Peptides and Activities
- Heavy Metal Exposure and Toxicity
- Air Quality and Health Impacts
- Inhalation and Respiratory Drug Delivery
- SARS-CoV-2 and COVID-19 Research
- Protein Tyrosine Phosphatases
Isabela State University
2023
Dartmouth College
2007-2020
Dartmouth–Hitchcock Medical Center
2009-2020
Bipar
2013
Yale University
2004-2008
VA Connecticut Healthcare System
2005-2008
University of Virginia
1992-2005
Ghent University
2005
Ghent University Hospital
2005
Medizinische Hochschule Hannover
2004
Acute lung injury due to influenza infection is associated with high mortality, an increase in neutrophils the airspace, and increases tissue myeloperoxidase (MPO). Because IL-17A IL-17F, ligands for IL-17 receptor antagonist (IL-17RA), have been shown mediate neutrophil migration into response LPS or Gram-negative bacterial pneumonia, we hypothesized that IL-17RA signaling was critical acute pulmonary infection. weight loss both (MPO) after However, dispensable recruitment of CD8(+) T cells...
Staphylococcus aureus is a significant cause of hospital and community acquired pneumonia causes secondary infection after influenza A. Recently, patients with hyper-IgE syndrome, who often present S. infections the lung skin, were found to have mutations in STAT3, required for Th17 immunity, suggesting potential critical role cells pneumonia. Indeed, IL-17R(-/-) IL-22(-/-) mice displayed impaired bacterial clearance compared that wild-type mice. Mice challenged A PR/8/34 H1N1 subsequently...
Influenza infection is widespread in the United States and world. Despite low mortality rates due to infection, morbidity common little known about molecular events involved recovery. results persistent distal lung remodeling, mechanism(s) are poorly understood. Recently IL-22 has been found mediate epithelial repair. We propose that critical for recovery of normal function architecture after influenza infection. Wild-type IL-22(-/-) mice were infected with A PR8/34 H1N1 followed up 21 days...
Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody binds to and inhibits connective tissue growth factor activity) attenuated progression without substantial events.
Viral infections have more severe consequences in patients who been exposed to cigarette smoke (CS) than those not CS. For example, chronic obstructive pulmonary disease (COPD), viruses cause exacerbation, heightened inflammation, and accelerated loss of lung function compared with other causes exacerbation. Symptomatology mortality influenza-infected smokers is also enhanced. To test the hypothesis that these outcomes are caused by CS-induced alterations innate immunity, we defined effects...
BackgroundArsenic exposure is a significant worldwide environmental health concern. We recently reported that 5-week to environmentally relevant levels (10 and 100 ppb) of As in drinking water significantly altered components the innate immune response mouse lung, which we hypothesize an important contributor increased risk lung disease exposed human populations.ObjectivesWe investigated effects on respiratory influenza A (H1N1) virus infection, common potentially fatal disease.MethodsIn...
Influenza A represents a significant cause of morbidity and mortality worldwide.Bacterial complications influenza confer the greatest risk to patients.T H 17 pathway inhibition has been implicated as mechanism by which alters bacterial host defense.Here we show that preceding causes persistent Staphylococcus aureus infection suppression T activation in mice.Influenza does not inhibit S. binding uptake phagocytic cells but instead attenuates induced related antimicrobial peptides necessary...
Suppression of type 17 immunity by I interferon (IFN) during influenza A infection has been shown to enhance susceptibility secondary bacterial pneumonia. Although this mechanism described in coinfection with gram-positive bacteria, it is unclear whether similar mechanisms may impair lung defense against gram-negative infections. Furthermore, precise delineation the duration IFN-associated remains underexplored. Therefore, we investigated effects preceding virus on subsequent challenge...
Pneumonia is a leading cause of death worldwide. Staphylococcal aureus can be severe pneumonia alone or common pathogen in secondary following influenza. Recently, we reported that preceding influenza attenuated the Type 17 pathway, increasing lung's susceptibility to infection. IL-1β known regulate host defense, including playing role Th17 polarization. We examined whether signaling required for S. defense and infection impacted aureus-induced production subsequent pathway activation. Mice...
Influenza A virus (IAV) is a leading cause of respiratory tract disease worldwide. Anti-viral CD8+ T lymphocytes responding to IAV infection are believed eliminate virally infected cells by direct cytolysis but may also contribute pulmonary inflammation and tissue damage via the release pro-inflammatory mediators following recognition viral antigen displaying cells. We have previously demonstrated that expressing inflammatory hematopoietic origin within lung interstitium serve as presenting...
Arsenic has been linked to disrupted immune function and greater infection susceptibility in highly exposed populations. Well arsenic levels above the U.S. EPA limit occur our study area are of particular concern for pregnant women infants.We investigated whether utero exposure affects risk infections respiratory symptoms over first year life.We prospectively obtained information on infant symptoms, including their duration treatment (n = 412) at 4, 8, 12 months using a parental telephone...
Abstract Respiratory virus infection results in considerable pulmonary immunopathology, a component of which from the host immune responses. We have developed murine model to specifically examine lung injury due CD8+ T cell recognition an influenza hemagglutinin (HA) transgene on epithelium absence replicating virus, after adoptive transfer. Lung is largely mediated by chemokines expressed epithelial cells upon TNF-α. To determine critical source TNF-α, HA-specific TNF−/− were transferred...
Arsenic (As) exposure is a significant worldwide environmental health concern. Chronic via contaminated drinking water has been associated with an increased incidence of number diseases, including reproductive and developmental effects. The goal this study was to identify adverse outcomes in mouse model early life low-dose As (10 ppb, current U.S. EPA Maximum Contaminant Level).C57B6/J pups were exposed 10 ppb As, the dam her water, either utero and/or during postnatal period. Birth...
Influenza is a common respiratory virus and Staphylococcus aureus frequently causes secondary pneumonia during influenza infection, leading to increased morbidity mortality. has been found attenuate subsequent Type 17 immunity, enhancing susceptibility bacterial infections. IL-27 known inhibit suggesting potential critical role for in viral co-infection.A murine model of infection was used mimic human viral, co-infection. C57BL/6 wild-type, receptor α knock-out, IL-10 knock-out mice were...
CD8(+) T cells infiltrate the lung in many clinical conditions, particularly interstitial disease. The role(s) that might be playing pathogenesis of inflammatory disease is unclear at present, as direct contribution cell effector activities to injury. This report describes a transgenic model used evaluate impact, on respiratory structure and function, lymphocyte recognition target antigen expressed endogenously alveolar epithelial cells. We found adoptive transfer cloned cytotoxic...
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Influenza infection results in considerable pulmonary pathology, a significant component of which is mediated by CD8(+) T cell effector functions. To isolate the specific contribution cells to lung immunopathology, we utilized nonviral murine model alveolar epithelial express an influenza antigen and injury initiated adoptive transfer influenza-specific cells. We report that IFN-γ production adoptively transferred contributor acute following recognition, isolation from its impact on viral...
CD8+ T lymphocyte responses are a critical arm of the immune response to respiratory virus infection and may play role in pathogenesis interstitial lung disease. We have shown that cells induce significant injury absence by adoptive transfer into mice with alveolar expression viral transgene. The is characterized parenchymal infiltration host cells, primarily macrophages, which correlates physiologic deficits transgenic animals. cell–mediated can occur perforin Fas as long TNF-α available....
Tissue injury is a common sequela of acute virus infection localized to specific organ such as the lung. an immediate consequence with lytic viruses. It can also result from direct destruction infected cells by effector CD8+ T lymphocytes and indirectly through action cell–derived proinflammatory cytokines recruited inflammatory on uninfected tissue. We have examined cell–mediated pulmonary in transgenic model which adoptively transferred, virus-specific cytotoxic (CTLs) produce lethal,...
In a recent study of IFN-γ 1b in 330 patients with idiopathic pulmonary fibrosis (IPF), progression-free survival was unchanged; however, trend toward lower mortality seen 1b–treated compared placebo-treated (9.9 vs. 16.7%; p = 0.08). The purpose this randomized, double-blind, placebo-controlled trial to characterize molecular effects subcutaneous (200 μg) thrice weekly for 6 months versus placebo 32 IPF. Messenger RNA transbronchial lung biopsies and bronchoalveolar lavage cell pellet...
Abstract TNF-α is a pleotropic cytokine that has both proinflammatory and anti-inflammatory functions during influenza infection. first expressed as transmembrane protein proteolytically processed to release soluble form. Transmembrane (memTNF-α) (solTNF-α) have been shown exert distinct tissue-protective or tissue-pathologic effects in several disease models. However, the relative contributions of memTNF-α solTNF-α regulating pulmonary immunopathology following infection are unclear....