Jane Barnett
Pronouns: she/her
Research Mentor(s): Michal Olszewski
Research Mentor School/College/Department: Internal Medicine, Pulmonary and Critical Care Medicine / Medicine
Program:
Authors: Jane Barnett, Thalia Newman, Kristie Goughenhour, Rylan Hissong, Jintao Xu, Michal Olszewski
Session: Session 4: 1:40 pm – 2:30 pm
Poster: 55
Abstract
Cryptococcus neoformans (C.neo) is a fungal pathogen causing an opportunistic infection in immunocompromised individuals. Cryptococcal meningoencephalitis (CM) is the most severe type of infection, resulting in damage to the central nervous system (CNS), to which both the microbe and some of the host responses can contribute. Regulatory T cells (Treg) function is to “turn off” the excessive inflammation, and trigger repair of the inflamed tissues, and we propose they can reduce the brain damage in CM. Treg can produce the protein amphiregulin, (Areg), but the effects of Areg in cryptococcus infections are unknown. By creating mice with transgenic Tregs that can no longer produce Aregs, we hope to understand the role of Treg-produced Areg in CM. In transgenic Tamoxifen-inducible Foxp3creAregflox mice, selective depletion of Areg from Treg can be induced by treatment with the drug Tamoxifen. We hypothesized that CNS damage will be increased when we limit Treg production of Aregs. We use Foxp3creAregflox mice we intravenously infected with C.neo to induce CM. On days 10, 12, and 14 post-infection, we injected intraperitoneal doses of Tamoxifen. Finally, on day 21, we harvested the mice and observed changes in the immune environment. We observed these changes by completing flow cytometry, which showed only a partial reduction of Areg in Treg. This partial reduction of Areg, appeared not to cause significant differences in immune response between wild type and Areg fl/fl. However, there was an inverse correlation between Areg level in Treg, and inflammatory factor Tbet mean fluorescent intensity (MFI). This shows a potential link between Treg function and Areg and points toward the future direction of further optimizing tamoxifen dosing to obtain full depletion of Areg, which is likely to reduce the level of inflammatory response in the brain.
