Chloe Kazaglis
Pronouns: she/her
Research Mentor(s): Michal Olszewski
Research Mentor School/College/Department: Internal Medicine, Pulmonary and Critical Care Medicine / Medicine
Program: UROP
Session: Session 5 (2:40pm – 3:30pm)
Authors: Michal Olszewski, Chloe Kazaglis , Jintao Xu
Abstract
Cryptococcus neoformans is an opportunistic fungus found in the environment and causes lung infections, meningoencephalitis in individuals of compromised immunity. The fungi can cause significant mortality in HIV positive individuals with 200,000 deaths yearly. Current treatments and therapies for fungal infections are limited and highly toxic. Dendritic cells are a potential target for new immunotherapies, as they play an essential role in inducing adaptive immune response. In the immune system, dendritic cells are antigen presenting cells and producers of polarizing cytokines, which can stimulate naive helper T cells. Different subsets of dendritic cells can change the immune system’s strategy during infection response. Here, we focused on conventional dendritic cell 1 (cDC1) using a BATF3 knockout mouse model. Previous literature suggested mixed findings on the role of BATF3 dependent cDC1 in inducing Th1 response during bacterial and viral infections. Our study used a murine model of cryptococcal infection intravenously to approximate a disseminated infection, and intratracheally for a pulmonary infection. It was found that the absence of cDC1 in BATF3-/- mice resulted in decreased Th1 response with a lower percentage of CD4 T cells producing IFNg in both pulmonary and disseminated models. The BATF3-/- mice resulted in decreased fungal clearance, but no significant difference in survival. Next, we will explore the mechanisms of how cDC1 promotes Th1 response during Cryptococcal infection. This project will lead to potential therapeutic immunomodulations that will improve patient outcomes.
