Patrick Szygowski
Pronouns: He / Him
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: Patrck Szygowski, W. Rex Underwood, Kristie Goughenour, Jintao Xu, Michal Olszewski
Presenter: 71
Abstract
Cryptococcus neoformans is an environmental fungus that is an opportunistic infection, causing meningoencephalitis (1, 4). T cells have been found to play an integral role in the fungal clearance of Cryptococcus neoformans in the brain, but also to drive immunopathology in the infected brain (1, 4). A subset of T cells, regulatory T cells (Tregs) are crucial in reducing T cell-mediated immune responses, suppressing inflammation and promoting tissue repair (2). Amphiregulin is a protein produced by Tregs that acts as a growth factor. It can induce cell differentiation and suppress CD4+ T cells (5). The aim of this study is to determine if amphiregulin protects mice from immune-mediated inflammation and pathology during cryptococcus meningoencephalitis. To modulate the expression and production of amphiregulin, we used the tamoxifen-inducible cre flox system to delete the amphiregulin gene specifically in Treg cells (3). We test if amphiregulin depletion in Tregs increases brain immunopathology such as neuronal death, and enhances brain immune response as well as fungal clearance during cryptococcal meningoencephalitis. Our study shows that deletion of amphiregulin from Treg reduced infected mice survival rate with the areg depleted mice had a final survival rate of 25% while the control mice had a final survival rate of 75%. Areg depleted mice showed increased weight loss, and deleted fungal clearance. To address the mechanism of immune-mediated pathology we compared the magnitude of inflammatory response using multiple parameters but found no effect. The data collected supports our hypothesis that amphiregulin produced by Treg in the brain protects mice from cryptococcal meningoencephalitis, by improving fungal elimination but not via anti-inflammatory mechanisms. The alternative mechanisms by which Areg improves CNS health, such as tissue repair during meningitis is under investigation. 1: C. neoformans Infection Statistics. May 26, 2020. Centers for Disease Control and Prevention. https://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/statistics.html 2: Gulati, P. (2009), Janeway’s Immunobiology, 7th Edition by Kenneth Murphy, Paul Travers, and Mark Walport. Biochem. Mol. Biol. Educ., 37: 134-134. https://doi.org/10.1002/bmb.20272 3:Kim, H., Kim, M., Im, S. K., & Fang, S. (2018). Mouse Cre-LoxP system: general principles to determine tissue-specific roles of target genes. Laboratory animal research, 34(4), 147–159. https://doi.org/10.5625/lar.2018.34.4.147 4: Neal LM, Xing E, Xu J, Kolbe JL, Osterholzer JJ, Segal BM, Williamson PR, Olszewski MA. 2017. CD4+ T cells orchestrate lethal immune pathology despite fungal clearance during Cryptococcus neoformans meningoencephalitis. mBio 8:e01415-17. https://doi.org/10.1128/mBio.01415-17. 5:Zaiss DMW, Gause WC, Osborne LC, Artis D. Emerging functions of amphiregulin in orchestrating immunity, inflammation, and tissue repair. Immunity. 2015 Feb 17;42(2):216-226. doi: 10.1016/j.immuni.2015.01.020.
Biomedical Sciences, Interdisciplinary, Natural/Life Sciences
