Dissertations and Theses
Date of Award
2020
Document Type
Thesis
Department
Biology
First Advisor
Lucia Fuentes
Second Advisor
Maria Entezari
Third Advisor
Bao Vuong
Keywords
Alzehimers, C.albicans, Phagocytosis, Microglia, VIPER, Anti-inflammatory
Abstract
Microglia cells are the first line of innate immunity defense in the central nervous system (CNS). They play a critical role in maintaining CNS homeostasis by having an active but yet balanced phagocytic activity. However, in various CNS related diseases, microglia cells have been shown to malfunction. In Alzheimer's Disease (AD), hyperactive microglia with impaired phagocytic activity is the main hallmark of this disease, along with the accumulation of amyloid-beta aggregates. Additionally, emerging new studies have suggested a fungal infection etiology to AD, specifically in relation to Candida albicans (C.albicans). Thus, understanding the mechanism of fungal clearance in the CNS is of importance. The main pathogen-associated molecular pattern (PAMP) for Candida is its fungal cell wall, which consists of structural carbohydrates β-1,3 glucan and O-mannan, recognized by pattern recognition receptors (PRR) β-glucan receptors found on the surface of microglia. In this study, we showed that the pro-inflammatory PAMP Lipopolysaccharide (LPS) causes an upregulation in zymosan phagocytosis, a fungal cell wall extract from Saccharomyces cerevisiae in microglia like BV2 cells. Furthermore, we examined the possible involvement of a β-glucan receptor on zymosan phagocytosis using laminarin, a soluble β-glucan molecule. In addition, we investigated the potential impact of TLR-4' The LPS receptor' on zymosan phagocytosis by treating BV2 cells with a TLR-4 viral inhibitor (VIPER) or a TLR-4 polyclonal antibody showing their antagonistic effects on phagocytosis. Finally, we demonstrated that VIPER has the unique ability to upregulate zymosan phagocytosis while blocking TLR-4 activity in microglia.
Recommended Citation
Alzeory, Sherouk, "LPS, A TLR-4 AGONIST AND VIPER A TLR-4 INHIBITOR UPREGULATE PHAGOCYTOSIS OF ZYMOSAN IN BV2 CELLS" (2020). CUNY Academic Works.
https://academicworks.cuny.edu/cc_etds_theses/845