A5066386290- IL-33, ST2, and ILC Pathways
- Immune Cell Function and Interaction
- Eosinophilic Esophagitis
- Asthma and respiratory diseases
- Antifungal resistance and susceptibility
- Clostridium difficile and Clostridium perfringens research
- Antimicrobial Resistance in Staphylococcus
- Antibiotic Resistance in Bacteria
- Inhalation and Respiratory Drug Delivery
- Toxin Mechanisms and Immunotoxins
- Viral Infections and Vectors
- Vector-borne infectious diseases
- Streptococcal Infections and Treatments
- Nosocomial Infections in ICU
- Pediatric health and respiratory diseases
- Monoclonal and Polyclonal Antibodies Research
- Antimicrobial Peptides and Activities
- Antibiotics Pharmacokinetics and Efficacy
- Abdominal Trauma and Injuries
- Vector-Borne Animal Diseases
- Immune Response and Inflammation
- Pneumonia and Respiratory Infections
- Transgenic Plants and Applications
- Yersinia bacterium, plague, ectoparasites research
- Immunodeficiency and Autoimmune Disorders
University of California, San Francisco
2017-2023
University of California, Davis
2020-2023
University of Ulsan
2012-2021
Australian National University
2016
Abstract IL-33 is known to play an important role in Th2 immunity. In this study, we investigated the effect of pretreatment on anti-fungal response using acute Candida albicans peritoneal infection model. induced a rapid fungal clearance and markedly reduced C. infection-associated mortality. The priming occurred during multiple steps neutrophil-mediated response. First, due massive recruitment neutrophils site as result release CXCR2 chemokines by macrophages reversal TLR-induced reduction...
The role broad-spectrum antibiotics play in the spread of antimicrobial resistance, coupled with their effect on healthy microbiome, has led to advances pathogen-specific approaches for prevention or treatment serious bacterial infections. One approach clinical testing is passive immunization a monoclonal antibody (MAb) targeting alpha toxin Staphylococcus aureus pneumonia. Passive human anti-alpha MAb, MEDI4893*, been shown improve disease outcome murine S. pneumonia models. species...
Pseudomonas aeruginosa is among the most formidable antibiotic-resistant pathogens and a leading cause of hospital-associated infections. With dwindling options for infections, new paradigm treatment disease resolution required. MEDI3902, bispecific antibody targeting P. type III secretion (T3S) protein PcrV Psl exopolysaccharide, was previously shown to mediate potent protective activity in murine infection models. current challenges associated with clinical development narrow-spectrum...
Abstract Staphylococcus aureus is a common pathogen causing infections in humans with various degrees of severity, pneumonia being one the most severe infections. In as much staphylococcal disease driven large part by α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL), we evaluated whether active immunization attenuated forms Hla (HlaH35L/H48L) alone, PVL components (LukS-PVT28F/K97A/S209A LukF-PVK102A) or combination all 3 toxoids could prevent lethal challenge rabbit model necrotizing...
IL-33 has been implicated in the pathogenesis of asthma, atopic allergy, anaphylaxis, and other inflammatory diseases by promoting production proinflammatory cytokines chemokines or Th2 immune responses. In this study, we analyzed vivo effect administration. markedly promoted myelopoiesis bone marrow myeloid cell emigration. Concomitantly, induced hematopoietic stem progenitor (HSPC) mobilization extramedullary hematopoiesis. HSPC was mediated mainly through increased levels CCL7 produced...
Pseudomonas aeruginosa is a challenge for clinicians due to increasing drug resistance and dwindling treatment options. We report on the activity of MEDI3902, an antibody targeting type 3 secretion protein PcrV Psl exopolysaccharide, in rabbit bloodstream lung infection models. MEDI3902 prophylaxis or was protective both acute models exhibited enhanced when combined with subtherapeutic dose meropenem.
Susceptibility to systemic Candida albicans infection is determined by immune resistance, as well the ability control Candida-induced immunopathologies. We showed previously that exogenous IL-33 can increase resistance peritoneal C. regulating multiple steps of neutrophil anti-Candida response. In this study, using a mouse model candidiasis, we observed administration limited fungal burden and inflammation increased survival. kidneys, seemed directly act on neutrophils CD4(+) T cells:...
Staphylococcus aureus is a major human pathogen that causes wide range of infections by producing an arsenal cytotoxins. We found passive immunization with either monoclonal antibody (MAb) neutralizing alpha-hemolysin or broadly cross-reactive MAb Panton-Valentine leukocidin, leukocidin ED, and gamma-hemolysins HlgAB HlgCB conferred only partial protection, whereas the combination those two MAbs significant protection in rabbit model necrotizing pneumonia caused USA300 methicillin-resistant...
Abstract Infection with Borrelia burgdorferi causes Lyme disease in humans. In small rodents, the natural reservoir species of this spirochete, infections lead to only modest manifestations, despite causing persistence infection. Although B cell responses are central for controlling bacterial tissue burden and they lack classical aspects T-dependent responses, such as sustained IgG affinity maturation longevity, corresponding a rapid collapse germinal centers. Instead, Ab response is...
C-C chemokine receptor type 5 (CCR5) regulates the trafficking of various immune cells to sites infection. In this study, we showed that expression CCR5 and its ligands was rapidly increased in kidney after systemic Candida albicans infection, infected CCR5-/- mice exhibited mortality morbidity, indicating contributes an effective defense mechanism against C. The susceptibility infection due impaired fungal clearance, which turn resulted exacerbated renal inflammation damage. CCR5-mediated...
IL-33 is a member of the IL-1 cytokine family and plays role in host defense against bacteria, viruses, fungi.In this study, we investigated function its receptor vitro macrophage responses to Candida albicans.Our results demonstrate that pre-sensitization isolated peritoneal macrophages with enhanced their pro-inflammatory production phagocytic activity response C. albicans.These activities were entirely dependent on ST2-MyD88 signaling pathway.In addition, also increased ROS subsequent...
Invasive fungal infections by Candida albicans frequently cause mortality in immunocompromised patients. Neutrophils are particularly important for clearance during systemic C. albican infection, yet little has been known regarding which surface receptor controls neutrophils’ antifungal activities. CD137, is encoded Tnfrsf9, belongs to the tumor necrosis superfamily and shown regulate neutrophils Gram-positive bacterial infection. Here, we used genetic immunological tools probe involvement...
Ventilator-associated pneumonia is an important clinical manifestation of the nosocomial pathogen Pseudomonas aeruginosa. We characterized correlates protection with MEDI3902, a bispecific human IgG1 monoclonal antibody that targets P. aeruginosa type 3 secretion system PcrV protein and Psl exopolysaccharide, in rabbit model ventilator-associated using lung-protective, low-tidal-volume mechanical ventilation. Rabbits infused MEDI3902 prophylactically were protected, whereas those pretreated...
Abstract Long-lived T-dependent B cell responses fail to develop during persistent infection of mice with Borrelia burgdorferi, the causative agent Lyme disease, raising questions about induction and/or functionality anti–B. burgdorferi adaptive immune responses. Yet, a lack reagents has limited investigations into B. burgdorferi–specific T and cells. We attempted two approaches track burgdorferi–induced CD4 First, mutant was generated an influenza hemagglutinin (HA) peptide, HA111–119,...
Abstract Invasive candidiasis has high mortality rates in immunocompromised patients, causing serious health problems. In mouse models, innate immunity protects the host by rapidly mobilizing a variety of resistance and tolerance mechanisms to systemic Candida albicans infection. We have previously demonstrated that exogenous IL-33 regulates multiple steps involving processes. this study, we systematically analyzed vivo functions endogenous using Il33−/− mice vitro immune cell culture....
Background New drugs targeting antimicrobial resistant pathogens, including Pseudomonas aeruginosa , have been challenging to evaluate in clinical trials, particularly for the non-ventilated hospital-acquired pneumonia and ventilator-associated indications. Development of new antibacterial is facilitated by preclinical animal models that could predict efficacy patients with these infections. Methods We report here an FDA-funded study develop a rabbit model determining extent which natural...
Abstract CCR5 regulates the trafficking of various immune cells to site infection. Expression and its ligands were rapidly increased in kidney after systemic Candida albicans infection infected CCR5−/− mice showed mortality morbidity, indicating that contributes an effective defense mechanism against C. The susceptibility ablicans was due their impaired capacity fungal clearance, which turn resulted exacerbated renal inflammation damage. CCR5-mediated recruitment NK response necessary for...
Abstract Tick-borne infection with Borrelia burgdorferi (Bb) causes Lyme disease in humans and persistent of mice, its natural reservoir host. IgG responses critically control Bb tissue burden but do not clear the infection. We previously showed induction germinal centers (GC) mice after followed by their rapid collapse within 30 days, despite ongoing This was consistent lack long-lived high-affinity antibody these mice. Our recent experiments that serum from Bb-infected bound more strongly...