LPS, A TLR-4 AGONIST AND VIPER A TLR-4 INHIBITOR UPREGULATE PHAGOCYTOSIS OF ZYMOSAN IN BV2 CELLS

<p>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 <em>Candida albicans (C.albicans)</em>. Thus, understanding the mechanism of fungal clearance in the CNS is of importance. The main pathogen-associated molecular pattern (PAMP) for <em>Candida</em> 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.<strong> </strong>In<strong> </strong>this study, we showed that the pro-inflammatory PAMP Lipopolysaccharide (LPS) causes an upregulation in zymosan phagocytosis, a fungal cell wall extract from Saccharomyces<em> cerevisiae</em><em> </em>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. </p> <p><strong> </strong></p>

Name thesis:degree_name

Master of Science (M.S.)

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Biology

Year dc:date.available

2020

Author dc:creator

• Alzeory, Sherouk

Contributors dc:contributor

• Lucia Fuentes
• Maria Entezari
• Bao Vuong

• Alzehimers
• C.albicans
• Phagocytosis
• Microglia
• VIPER
• Anti-inflammatory
• Cell and Developmental Biology
• Cell Biology
• Other Immunology and Infectious Disease

Repository record dc:identifier

https://academicworks.cuny.edu/cc_etds_theses/845

OAI identifier oai:identifier

oai:academicworks.cuny.edu:cc_etds_theses-1952