A5019924125- Fungal Infections and Studies
- Immune Response and Inflammation
- Antifungal resistance and susceptibility
- Nail Diseases and Treatments
- Immunotherapy and Immune Responses
- Antimicrobial Peptides and Activities
- Immune Cell Function and Interaction
- Mycobacterium research and diagnosis
- IL-33, ST2, and ILC Pathways
- COVID-19 Clinical Research Studies
- Mast cells and histamine
- Toxin Mechanisms and Immunotoxins
- Venous Thromboembolism Diagnosis and Management
- Pediatric health and respiratory diseases
- NF-κB Signaling Pathways
- Asthma and respiratory diseases
- Eosinophilic Esophagitis
- Plant Pathogens and Fungal Diseases
- Plant Pathogens and Resistance
- Cytokine Signaling Pathways and Interactions
- Anesthesia and Neurotoxicity Research
- Long-Term Effects of COVID-19
- S100 Proteins and Annexins
- Glutathione Transferases and Polymorphisms
- Intensive Care Unit Cognitive Disorders
Paul Ehrlich Institut
2014-2021
Harvard University
2021
Massachusetts General Hospital
2020-2021
VA Ann Arbor Healthcare System
2016-2018
Michigan Medicine
2016-2018
Michigan United
2016
University of Michigan
2016
McGill University
2012-2015
McGill University Health Centre
2015
Christie (Canada)
2015
Susceptibility to progressive infection with the fungus Cryptococcus neoformans is associated an allergic pattern of lung inflammation, yet factors that govern this host response are not clearly understood. Using a clinically relevant mouse model inhalational virulent C. H99, we demonstrate role for IL-33-dependent signaling in immune defense. Infection BALB/c mice 10(4) CFU H99 caused time-dependent induction IL-33 accumulation type 2 pulmonary innate lymphoid cells and alternatively...
Abstract Background Monophosphoryl lipid A ( MPLA ), a nontoxic TLR 4 ligand derived from lipopolysaccharide LPS is used clinically as an adjuvant in cancer, hepatitis, and malaria vaccines allergen‐specific immunotherapy. Nevertheless, its cell‐activating effects have not been analyzed comprehensive direct comparison including wide range of different immune cells. Therefore, the objective this study was side‐by‐side immune‐modulating properties on Methods Immune‐activating were compared...
Abstract The scavenger receptor macrophage with collagenous structure (MARCO) promotes protective innate immunity against bacterial and parasitic infections; however, its role in host fungal pathogens, including the major human opportunistic pathogen Cryptococcus neoformans, remains unknown. Using a mouse model of C. neoformans infection, we demonstrated that MARCO deficiency leads to impaired control during afferent phase cryptococcal infection. Diminished containment MARCO−/− mice was...
ABSTRACT Anti-tumor necrosis factor alpha (anti-TNF-α) therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model cryptococcal infection, we investigated the mechanism by which disruption early TNF-α signaling results in development nonprotective immunity against C. . We found that transient depletion inhibited pulmonary clearance enhanced...
Background. The detoxified TLR4-ligand Monophosphoryl Lipid A (MPLA) is the first approved TLR-agonist used as adjuvant in licensed vaccines but has not yet been explored part of conjugated vaccines. Objective. To investigate immune-modulating properties a fusion protein consisting MPLA and Ovalbumin (MPLA : Ova). Results. Ova were chemically coupled by stable carbamate linkage. was highly pure without detectable product-related impurities either noncoupled or Ova. Light scattering analysis...
Postoperative delirium (POD) is an acute altered mental state commonly encountered after cardiac surgery. The pathophysiological mechanisms underlying POD remain unclear. We aimed to identify circulating proteins significantly major surgery with cardiopulmonary bypass (CPB). also enable inferences on associations POD.Serum and whole blood samples were collected before CPB (n = 16 patients; n 8 POD) again from the same patients postoperative day 1. All clinically evaluated for days 1-3. An...
Macrophage receptor with collagenous structure (MARCO) contributes to fungal containment during the early/innate phase of cryptococcal infection; however, its role in adaptive anti-fungal immunity remains unknown. Using a murine model cryptococcosis, we compared host immune responses wild-type and MARCO-/- mice throughout an extended time course post-infection. Unlike early infection, MARCO deficiency resulted improved pulmonary clearance diminished dissemination efferent phase. Improved...
Background . TLR ligands can promote Th1-biased immune responses, mimicking potent stimuli of viruses and bacteria. Aim To investigate the adjuvant properties dual TLR2/7 compared to those mixture both single ligands. Methods Dual ligands: CL401, CL413, CL531, including CL264 (TLR7-ligand) Pam 2 CysK 4 (TLR2-ligand), were used. Immune-modulatory capacity with individual alone or as a in mouse BMmDCs, BMmDC:TC cocultures, BMCMCs was assessed naïve mice model OVA-induced intestinal allergy....
Genetic factors that regulate the pathogenesis of pneumonia caused by fungus Cryptococcus neoformans are poorly understood. Through a phenotypic strain survey we observed inbred C3H/HeN mice develop significantly greater lung fungal burden than resistant CBA/J 4 weeks following intratracheal infection with C. ATCC 24067. The aim present study was to characterize inflammatory response pulmonary and identify genetic loci host defense. Following cryptococcal infection, demonstrated Th2 immune...
Developing new adjuvants/vaccines and better understanding their mode-of-action is an important task. To specifically improve birch pollen allergy treatment, we designed a fusion protein consisting of major allergen Betv1 conjugated to the TLR5-ligand flagellin (rFlaA:Betv1). This study investigates immune-modulatory effects rFlaA:Betv1 on airway epithelial cells. LA-4 mouse lung cells were stimulated with in presence/absence various inhibitors cytokine- chemokine secretion quantified by...
The genetic basis of natural susceptibility to progressive Cryptococcus neoformans infection is not well understood. Using C57BL/6 and CBA/J inbred mice, we previously identified three chromosomal regions associated with C. (Cnes1, Cnes2, Cnes3). To validate characterize the role Cnes2 during host response, constructed a congenic strain on background (B6.CBA-Cnes2). Phenotypic analysis B6.CBA-Cnes2 mice 35 days after showed significant reduction fungal burden in lungs spleen higher pulmonary...
Monophosphoryl lipid A (MPL) is a non-toxic TLR4 ligand, derived from Salmonella minnesota R595 (Re) lipopolysaccharide (LPS) by chemical modification. It clinically used as an adjuvant for cancer treatment (Fendrix®, Ceravix®) and allergen specific immunotherapy (Pollinex® Quattro, ORALVAC®). Nevertheless, reports on the mechanism of activity are limited. The aim this study was to compare immune modulating capacities MPL LPS in vitro. In both human murine lung epithelial cell lines...
Abstract Resistance to the opportunistic fungal pathogen Cryptococcus neoformans (Cn) is associated with development of Th1/Th17 immune bias while a Th2 response results in increased susceptibility. Macrophage Receptor Collagenous Structure (MARCO) important for recognition some pathogens and subsequent activation polarization responses by DC macrophages, however, its role during Cn infection remains unknown. Here we found that spite diminished early (innate) control infected lungs,...
Abstract Cryptococcus neoformans is a common opportunistic pathogen that requires intact T cell-mediated immunity for protective host defenses. While Th1/Th17 responses contribute to the effective containment and elimination of C. neoformans, Th2 are non-protective can worsen clearance outcomes. Previous studies showed early tumor necrosis factor alpha (TNFα) signaling required optimal clearance, while its absence leads immune dysregulation persistent fungal infection. To determine...