A5004410792- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Immune Cell Function and Interaction
- Polysaccharides and Plant Cell Walls
- Immunotherapy and Immune Responses
- Galectins and Cancer Biology
- Immune Response and Inflammation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- T-cell and B-cell Immunology
- Glycosylation and Glycoproteins Research
- Plant-Microbe Interactions and Immunity
- Invertebrate Immune Response Mechanisms
- Asthma and respiratory diseases
- Mycobacterium research and diagnosis
- Immune cells in cancer
- Escherichia coli research studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Tuberculosis Research and Epidemiology
- Infectious Diseases and Mycology
- Antimicrobial Peptides and Activities
- Gut microbiota and health
- Immune responses and vaccinations
- Complement system in diseases
- Microbial Metabolites in Food Biotechnology
- Pediatric health and respiratory diseases
University of Exeter
2012-2025
University of Cape Town
2013-2025
University of Aberdeen
2015-2024
Wellcome Centre for Infectious Diseases Research in Africa
2009-2024
Medical Research Council
2017-2024
Colorado State University
2024
Harvard University
2023
Massachusetts General Hospital
2023
MRC Centre for Medical Mycology
2020
Institute of Medical Sciences
2011-2019
The ability of fungal-derived β-glucan particles to induce leukocyte activation and the production inflammatory mediators, such as tumor necrosis factor (TNF)-α, is a well characterized phenomenon. Although efforts have been made understand how these carbohydrate polymers exert their immunomodulatory effects, receptors involved in generating responses are unknown. Here we show that Dectin-1 mediates TNF-α response zymosan live fungal pathogens, an activity occurs at cell surface requires...
The intestinal microflora, typically equated with bacteria, influences diseases such as obesity and inflammatory bowel disease. Here, we show that the mammalian gut contains a rich fungal community interacts immune system through innate receptor Dectin-1. Mice lacking Dectin-1 exhibited increased susceptibility to chemically induced colitis, which was result of altered responses indigenous fungi. In humans, identified polymorphism in gene for (CLEC7A) is strongly linked severe form...
Zymosan is a β-glucan– and mannan-rich particle that widely used as cellular activator for examining the numerous responses effected by phagocytes. The macrophage mannose receptor (MR) complement 3 (CR3) have historically been considered major lectins involved in nonopsonic recognition of these yeast-derived particles. Using specific carbohydrate inhibitors, we show β-glucan receptor, but not MR, predominant this process. Furthermore, zymosan binding was unaffected genetic CD11b deficiency...
Mucocutaneous fungal infections are typically found in patients who have no known immune defects. We describe a family which four women were affected by either recurrent vulvovaginal candidiasis or onychomycosis had the early-stop-codon mutation Tyr238X beta-glucan receptor dectin-1. The mutated form of dectin-1 was poorly expressed, did not mediate binding, and led to defective production cytokines (interleukin-17, tumor necrosis factor, interleukin-6) after stimulation with Candida...
We recently identified dectin-1 (betaGR) as a major beta-glucan receptor on leukocytes and demonstrated that it played significant role in the non-opsonic recognition of soluble particulate beta-glucans. Using novel mAb (2A11) raised against betaGR, we show here is not dendritic cell-restricted first reported, but broadly expressed, with highest surface expression populations myeloid cells (monocyte/macrophage (Mphi) neutrophil lineages). Dendritic subpopulation T also expressed at lower...
Alveolar macrophages represent a first-line innate host defense mechanism for clearing inhaled Aspergillus fumigatus from the lungs, yet contradictory data exist as to which alveolar macrophage recognition receptor is critical immunity A. fumigatus. Acknowledging that cell wall contains high beta-1,3–glucan content, we questioned whether beta-glucan dectin-1 played role in this process. Monoclonal antibody, soluble receptor, and competitive carbohydrate blockage indicated inflammatory...
Abstract The mycobacterial cord factor trehalose-6,6-dimycolate (TDM) and its synthetic analog trehalose-6,6-dibehenate (TDB) are potent adjuvants for Th1/Th17 vaccination that activate Syk-Card9 signaling in APCs. In this study, we have further investigated the molecular mechanism of innate immune activation by TDM TDB. Syk-coupling adapter protein FcRγ was essential macrophage Th17 adjuvanticity. FcRγ-associated C-type lectin receptor Mincle expressed macrophages upregulated Recombinant...
A combination of genetic and environmental factors can cause autoimmune disease in animals. SKG mice, which are genetically prone to develop arthritis, fail the under a microbially clean condition, despite active thymic production arthritogenic T cells their persistence periphery. However, environment, single intraperitoneal injection zymosan, crude fungal beta-glucan, or purified beta-glucans such as curdlan laminarin trigger severe chronic arthritis but only transient normal mice. Blockade...