A5002939091- Immune Response and Inflammation
- Pneumonia and Respiratory Infections
- Neonatal Respiratory Health Research
- Immune Cell Function and Interaction
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- NF-κB Signaling Pathways
- Cytokine Signaling Pathways and Interactions
- Respiratory Support and Mechanisms
- RNA modifications and cancer
- Immune cells in cancer
- Chemokine receptors and signaling
- Atherosclerosis and Cardiovascular Diseases
- IL-33, ST2, and ILC Pathways
- RNA Research and Splicing
- Sepsis Diagnosis and Treatment
- interferon and immune responses
- Inflammation biomarkers and pathways
- Immune responses and vaccinations
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Influenza Virus Research Studies
- Inflammatory mediators and NSAID effects
- Mycobacterium research and diagnosis
- Inhalation and Respiratory Drug Delivery
- Pneumocystis jirovecii pneumonia detection and treatment
- MicroRNA in disease regulation
Boston University
2015-2025
University of Massachusetts Chan Medical School
2022-2025
Pulmonary Associates
2014-2022
Emory University Hospital
2015-2022
Kingston University
2022
Czech Academy of Sciences, Institute of Microbiology
2020-2021
University School
2010
Harvard University
2006-2009
Louisiana State University Health Sciences Center New Orleans
2001-2006
Czech Academy of Sciences, Institute of Physiology
2004-2005
Interleukin (IL)-23 is a heterodimeric cytokine that shares the identical p40 subunit as IL-12 but exhibits unique p19 similar to p35. IL-12/23 p40, interferon γ (IFN-γ), and IL-17 are critical for host defense against Klebsiella pneumoniae. In vitro, K. pneumoniae–pulsed dendritic cell culture supernatants elicit T production in IL-23–dependent manner. However, importance of IL-23 during vivo pulmonary challenge unknown. We show p40–deficient mice exquisitely sensitive intrapulmonary...
Abstract Local production of IL-17 is a significant factor in effective host defense against Gram-negative bacteria. However, the proximal events mediating elaboration by T cells remain unclear. In this study, we show vivo that intact Toll-like receptor 4 signaling lung required for induction both p19 transcript IL-23 and protein response to Klebsiella pneumoniae. Although widely considered CD4+ cell product, also demonstrate vitro CD8+ after culture medium from dendritic exposed these The...
Lung-resident memory B cells (BRM cells) are elicited after influenza infections of mice, but connections to other pathogens and hosts — as well their functional significance have yet be determined. We postulate that BRM core components lung immunity. To test this, we examined whether by the respiratory pathogen pneumococcus, present in humans, important pneumonia defense. Lungs mice had recovered from pneumococcal did not contain organized tertiary lymphoid organs, plasma noncirculating...
Abstract Barrier tissues are populated by functionally plastic CD4 + resident memory T (T RM ) cells. Whether the barrier epithelium regulates cell locations, plasticity and activities remains unclear. Here we report that lung epithelial cells, including distinct surfactant protein C (SPC) low MHC high function as anatomically-segregated temporally-dynamic antigen presenting In vivo ablation of MHC-II results in altered localization Recurrent encounters with cognate absence leads cells to...
Patients afflicted with Stimulator of interferon gene (STING) gain-of-function mutations frequently present debilitating interstitial lung disease (ILD) that is recapitulated in mice expressing the STING
While signal transducer and activator of transcription (STAT) 3 signaling has been linked to multiple pathways influencing immune function cell survival, the direct influence this factor on innate immunity tissue homeostasis during pneumonia is unknown. Human patients with dominant-negative mutations in Stat3 gene develop recurrent pneumonias, suggesting a role for STAT3 pulmonary host defense. We hypothesized that alveolar epithelial activated by IL-6 family cytokines required effective...
Abstract Eradication of bacteria in the lower respiratory tract depends on coordinated expression proinflammatory cytokines and consequent neutrophilic inflammation. To determine roles NF-κB subunit RelA facilitating these events, we infected RelA-deficient mice (generated a TNFR1-deficient background) with Streptococcus pneumoniae. deficiency decreased cytokine expression, alveolar neutrophil emigration, lung bacterial killing. S. pneumoniae killing was also diminished lungs expressing...
Pneumonia results from bacteria in the alveoli. The alveolar epithelium consists of type II cells, which secrete surfactant and associated proteins, I constitute 95% surface area meet anatomic structural needs. Other than constitutively expressed it is unknown whether epithelial cells have distinct roles innate immunity. Because immunity gene induction depends on NF-κB RelA (also known as p65) during pneumonia, we generated a murine model mutated throughout epithelium. In response to LPS,...
The acute phase response is an evolutionarily conserved reaction in which physiological stress triggers the liver to remodel blood proteome. Although thought be involved immune defense, net biological effect of remains unknown. As stimulated by diverse cytokines that activate either NF-κB or STAT3, we hypothesized it could eliminated hepatocyte-specific interruption both transcription factors. Here, report elimination mice p65 (RelA) and but neither alone, abrogated all responses measured....
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Community-acquired pneumonia is a widespread disease with significant morbidity and mortality. Alveolar macrophages are tissue-resident lung cells that play crucial role in innate immunity against bacteria cause pneumonia. We hypothesized alveolar display adaptive characteristics after resolution of bacterial studied mice 1 to 6 months self-limiting infections Streptococcus pneumoniae, the most common macrophages, but not other myeloid cells, recovered from showed long-term modifications...
Interleukin (IL)-6 concentrations are positively associated with the severity of pneumonia, and this cytokine is essential to surviving experimental pneumococcal pneumonia. The role that IL-6 plays during pneumonia its impact gram-negative bacterial remain be determined. During Escherichia coli IL-6-deficient mice had increased burdens in their lungs, indicating compromised host defenses. Decreased neutrophil counts alveolar air spaces, despite normal blood survival emigrated neutrophils,...
Lung infections represent a tremendous disease burden and leading cause of acute lung injury. STAT3 signaling is essential for controlling injury during pneumonia. We previously identified LIF as prominent STAT3-activating cytokine expressed in the airspaces pneumonic lungs, but its physiological significance this setting has never been explored. To do so, Escherichia coli was intratracheally instilled into C57BL/6 mice presence neutralizing anti-LIF IgG or control IgG. Anti-LIF completely...
Background: Acute alcohol intoxication impairs neutrophil migration in response to intrapulmonary infection with Streptococcus pneumoniae , the most common bacterial cause of pneumonia. Many same host defense functions that are impaired alcohol‐intoxicated mechanistically associated chemokines, a group proinflammatory molecules enhance adhesion and direct sites inflammation. The purpose this study was determine whether alcohol‐induced chemokine suppression is responsible for recruitment into...
ABSTRACT The acute-phase response is characterized by increased circulating levels of proteins (APPs) generated the liver. During bacterial pneumonia, APPs correlate with severity disease, serve as biomarkers, and are functionally significant. kinetics regulatory mechanisms APP induction in liver during lung infection have yet to be defined. Here we show that mRNA transcription induced livers mice whose lungs infected either Escherichia coli or Streptococcus pneumoniae , both cases this...
The Zcchc11 enzyme is implicated in microRNA (miRNA) regulation. It can uridylate let-7 precursors to decrease quantities of the mature miRNA embryonic stem cell lines, suggested mediate maintenance. miR-26 relieve silencing activity without impacting content cancer cytokine and growth factor expression. Broader roles shaping or remodeling miRNome directing biological physiological processes remain entirely speculative. We generated Zcchc11-deficient mice address these knowledge gaps....
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