A5007701484- Tuberculosis Research and Epidemiology
- Immune Response and Inflammation
- Mycobacterium research and diagnosis
- Influenza Virus Research Studies
- Immunodeficiency and Autoimmune Disorders
- Psoriasis: Treatment and Pathogenesis
- Respiratory viral infections research
- Pediatric health and respiratory diseases
- Atherosclerosis and Cardiovascular Diseases
- Toxoplasma gondii Research Studies
- Helicobacter pylori-related gastroenterology studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Immune cells in cancer
- interferon and immune responses
- Trace Elements in Health
- Herpesvirus Infections and Treatments
- Antimicrobial Resistance in Staphylococcus
- Viral Infections and Immunology Research
- Metabolism, Diabetes, and Cancer
- Peroxisome Proliferator-Activated Receptors
- Infectious Diseases and Tuberculosis
- Diabetes Treatment and Management
- Immunotherapy and Immune Responses
- Immune responses and vaccinations
- Acute Kidney Injury Research
Children's Hospital of Pittsburgh
2014-2025
University of Pittsburgh
2010-2024
University of Pittsburgh Medical Center
2014-2023
Richard King Mellon Foundation
2016-2017
MGH Institute of Health Professions
2017
Broad Institute
2017
Charité - Universitätsmedizin Berlin
2017
Universitätsmedizin Greifswald
2017
University of Pennsylvania
2017
University of California, San Francisco
2017
Mycobacterium tuberculosis (Mtb), the causative agent of (TB), infects one third world's population. Among these infections, clinical isolates belonging to W-Beijing appear be emerging, representing about 50% Mtb in East Asia, and 13% all worldwide. In animal models, infection with strain, HN878, is considered “hypervirulent” as it results increased mortality causes exacerbated immunopathology infected animals. We had previously shown Interleukin (IL) -17 pathway dispensable for primary...
One third of the world's population is infected with Mycobacterium tuberculosis (Mtb). Although most people remain asymptomatic, they have a 10% lifetime risk developing active (TB). Thus, current challenge to identify immune parameters that distinguish individuals latent TB from those TB. Using human and experimental models Mtb infection, we demonstrated organized ectopic lymphoid structures containing CXCR5+ T cells were present in Mtb-infected lungs. In addition, found infection models,...
Rationale: A hallmark of pulmonary tuberculosis (TB) is the formation granulomas. However, immune factors that drive a protective granuloma during latent TB, and inflammatory granulomas active are not well defined.Objectives: The objective this study was to identify underlying mechanisms involved in seen TB.Methods: mediators TB were assessed using human samples experimental models Mycobacterium infection, molecular immunologic techniques.Measurements Main Results: We demonstrate patients...
IL-23 is required for the IL-17 response to infection with Mycobacterium tuberculosis, but not early control of bacterial growth. However, mice deficient p19 component (Il23a(-/-)) exhibit increased growth late in that temporally associated smaller B cell follicles lungs. Cxcl13 follicle formation and immunity during tuberculosis. The absence results decreased expression within M. tuberculosis-induced lymphocyte lungs, this deficiency was cuffing T cells around vessels lungs these mice....
The generation of effective type 1 T helper (Th1)-cell responses is required for immunity against intracellular bacteria. However, some bacteria require interleukin (IL)-17 to drive Th1-cell and subsequent protective host immunity. Here, in a model Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccination mice, we demonstrate that the dependence on IL-17 mechanism overcome bacteria-induced IL-10 inhibitory effects. We show BCG-induced prostaglandin-E2 (PGE2) promotes production which...
The variable efficacy of tuberculosis (TB) vaccines and the emergence drug-resistant strains Mycobacterium (Mtb) emphasize urgency for not only generating new more effective against TB but also understanding underlying mechanisms that mediate vaccine-induced protection. We demonstrate mucosal adjuvants, such as type II heat labile enterotoxin (LT-IIb), delivered through route induce pulmonary Mtb-specific T helper 17 (Th17) responses provide protection Mtb infection. Importantly, is...
The development of a tuberculosis (TB) vaccine that induces sterilizing immunity to Mycobacterium infection has been elusive. Absence induced by TB vaccines may be due delayed activation mucosal dendritic cells (DCs), and subsequent delay in antigen presentation vaccine-induced CD4+ T-cell responses. Here we show pulmonary delivery activated M. antigen-primed DCs into vaccinated mice, at the time exposure, can overcome accumulation In addition, activating endogenous host CD103+ CD40-CD40L...
Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that coinfections contribute to increased TB susceptibility and rates reactivation. Prevailing models T helper type 2 (Th2) responses induced by infection impair Th1 immune thereby limit Mycobacterium (Mtb) control. Using pulmonary mouse model Mtb infection, we demonstrated S. mansoni coinfection or immunization egg antigens can...
Pulmonary tuberculosis (TB), caused by the intracellular bacteria Mycobacterium tuberculosis, is a worldwide disease that continues to kill more than 1.5 million people every year worldwide. The accumulation of lymphocytes mediates formation tubercle granuloma in lung and crucial for host protection against M.tuberculosis infection. However, paradoxically also basis immunopathology associated with very little known about regulatory mechanisms constrain inflammation granulomas. Lipocalin 2...
Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark pulmonary (TB) formation hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, granulomas are associated with increased disease severity and provide niche for However, host immune responses that promote development TB not well described. Using Mtb mouse model, we show loss virulence factors, such as phenolic glycolipids,...
Chronic lower respiratory diseases (CLRD) increase the risk of type 2 diabetes, which in turn may worsen lung function. Metformin, a common antidiabetic with anti-inflammatory and antioxidant properties, improve outcomes. Therefore, we examined association metformin use mortality from CLRD.
Influenza is a common respiratory virus that infects between 5 and 20% of the US population results in 30,000 deaths annually. A primary cause influenza-associated death secondary bacterial pneumonia. We have previously shown influenza induces type I interferon (IFN)-mediated inhibition Type 17 immune responses, resulting exacerbation burden during
Abstract Influenza virus infects millions each year, contributing greatly to human morbidity and mortality. Upon viral infection, pathogen-associated molecular patterns activate pattern recognition receptors on host cells, triggering an immune response. The CD209 protein family, homologs of DC-SIGN (dendritic cell–specific intercellular adhesion molecule 3–grabbing nonintegrin), is thought modulate responses viruses. effects the mouse functional homolog CD209d/e lung during influenza...
Abstract Staphylococcus aureus is a commensal and opportunist pathogen of the upper respiratory tract. The recognition pathogen-associated molecular patterns through pattern-recognition receptors crucial for eliminating microorganisms such as S. aureus. DC-SIGN (CD209) receptor that binds to broad range pathogens, promoting phagocytosis. Here we aimed study role mouse homologues DC-SIGN, CD209d/e, in methicillin-resistant (MRSA) pulmonary infection model. CD209d/e−/− wild-type C57BL/6 mice...
Abstract Background The control of Mycobacterium tuberculosis (Mtb) infection begins with the recognition mycobacterial structural components by toll like receptors (TLRs) and other pattern receptors. Our objective was to determine influence TLRs polymorphisms in susceptibility develop (TB) Amerindian individuals from a rural area Oaxaca, Mexico high TB incidence. Methods We carried out case–control association community based study, genotyping 12 TLR2, TLR4, TLR6 TLR9 genes 90 patients...
Influenza is an annual, global health care concern. Secondary bacterial pneumonia a severe complication associated with primary influenza virus infection, often resulting in critical morbidity and mortality. Our laboratory has identified influenza-induced suppression of anti-bacterial Type 17 immunity as mechanism for enhanced susceptibility to super-infection. We have shown that type I interferon impairs activation. STAT1 transcription factor involved signaling, shared by I, II, III...
Mucosal vaccines are thought to confer superior protection against mucosal infectious diseases. In addition, routes of vaccine delivery preferentially induce the generation T helper 17 (Th17) cells, which produce cytokine IL-17. Th17 cells critical in mediating vaccine-induced immunity several However, IL-17 is also a potent proinflammatory cytokine, and we recently showed that mediates immunopathology lung injury after influenza infection mice. present study, tested hypothesis pre-exposure...
SUMMARY Intestinal epithelial cells (IECs) form a barrier between invading microorganisms and the underlying host tissues. IECs express toll‐like receptors (TLRs) that recognize specific molecular signatures on microbes, which activate intracellular signalling pathways leading to production of proinflammatory cytokines chemokines. Stress hormones play an important role in modulation down‐regulation immune responses. Here we demonstrated expression levels TLR‐2, TLR‐4, TLR‐9 TLR‐11 were...
Influenza virus is among the most common causes of respiratory illness worldwide and can be complicated by secondary bacterial pneumonia, a frequent cause mortality. When influenza infects lung, innate immune response activated, interferons inflammatory mediators are released. This "cytokine storm" thought to play role in influenza-induced lung pathogenesis. Peroxisome proliferator-activated receptor gamma (PPARγ) member nuclear hormone super-family. PPARγ has numerous functions including...
IL-10 production during intracellular bacterial infections is generally thought to be detrimental because of its role in suppressing protective T-helper cell 1 (Th1) responses. Francisella tularensis a facultative bacterium that activates both Th1 and Th17 immune Herein, we report IL-10–deficient mice (Il10−/−), despite having increased responses, exhibit mortality after pulmonary infection with F. live vaccine strain. We demonstrate the observed Il10−/−-infected due exacerbated IL-17 causes...
Significant morbidity in cystic fibrosis (CF) results from chronic lung inflammation, most commonly due to Pseudomonas aeruginosa infection. Recent data suggest that IL-17 contributes pathological inflammation the setting of abnormal mucosal immunity, and type 17 immunity–driven inflammatory responses may represent a target block aberrant CF. Indeed, transcriptomic analysis airway epithelium CF patients undergoing clinical bronchoscopy revealed upregulation downstream signature genes,...
Abstract Although zinc deficiency (secondary to malnutrition) has long been considered an important contributor morbidity and mortality of infectious disease (e.g. diarrhea disorders), epidemiologic data (including randomized controlled trials with supplemental zinc) for such a role in lower respiratory tract infection are somewhat ambiguous. In the current study, we provide first preclinical evidence demonstrating that although diet‐induced acute (Zn‐D: ~50% decrease) did not worsen induced...