Arianna Creech
Pronouns: She/her
Research Mentor(s): Michal Olszewski
Co-Presenter:
Research Mentor School/College/Department: Internal Medicine, Pulmonary and Critical Care Medicine / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 4 – 2:40pm – 3:30 pm
Room: League Ballroom
Authors: Arianna Creech, Jintao Xu, Kristie Goughenour, Michal Olszewski
Presenter: 73
Abstract
Cryptococcus neoformans is an opportunistic fungus found naturally in the environment and can cause severe meningoencephalitis, in both immunocompromised and competent individuls. Symptoms of patients mainly include headache, fever, and nausea, causing about 200,000 deaths yearly worldwide. Previously our laboratory found the immunological response to this infection can cause damage to the neuron cells in the brain and thus mediate disease pathology during cryptococcal meningoencephalitis. The overactive immune response ends up harming the central nervous system (CNS). To better understand how the immune cells cause tissue damage and disease pathology, a murine model was used where the mice were infected and observed for any physical signs of neurological dysfunction. This project focuses on the FAS-ligand (FASL) and FAS-receptor pathway. When the FAS-L binds to the FAS-receptor, it can induce programmed cell death and thus play important roles in immune responses to infections. In a previous experiment, we found that FAS-L was highly expressed by brain infiltrating CD4 T cells when significant brain damage was present. The hypothesis we are testing is whether FAS-L expression by T cells cause apoptosis of neuron cells and thus brain pathology during cryptococcal meningoencephalitis. To block this pathway, mice infected with cryptococcus neoformans given an anti-FAS-L antibody. We found that the mice treated with anti-FAS-L antibody lost less weight and survived better even though they had higher fungal burden in their brains. These results support our hypothesis that FASL plays a pathological role during the cryptococcal meningoencephalitis. Future studies are needed to specifically deplete FASL in T cells to evaluate its role in causing neuronal death and disease pathology. Our study thus may help to identify the FASL pathway as a potential target for interventions aimed to limit inflammatory CNS pathology in CM patients.
Biomedical Sciences, Interdisciplinary, Natural/Life Sciences
