Jasmine Chang
Research Mentor: Michal Olszewski
Mentor Department: Internal Medicine, Pulmonary and Critical Care Medicine, Medicine
Author(s): Jasmine Chang, Rylan Hissong, Hailong Li, Lauren Borhani, Maia Litner, Shelby Hopson, Kristie Goughenour, Jintao Xu, Michal Olszewski
Session: Session 1 (9:00 AM – 9:50 AM)
Presentation Type: Poster 98
Abstract
Cryptococcus neoformans meningoencephalitis (CM) is a lethal fungal disease with a strong inflammatory component. While the inflammation is driven by the effector T-cells producing INF-g and TNF-a inflammatory cytokines, there are also anti-inflammatory factors produced by regulatory T cells, which serve as the “brakes†of the immune system. One of such anti-inflammatory factors that Tregs can make is IL-10 cytokine, however its role in cryptococcal meningitis is unknown. We hypothesize that IL-10 restricts inflammation during CM and a murine model of CM is used to test this hypothesis. IL-10-/- and their wild type (WT) counterparts C57BL6 mice, were infected intravenously to induce CM. The outcomes were compared between the groups including weight loss and other symptoms, brain fungal burden, immune cell responses (flow cytometry) in the dispersed brains, and immunofluorescent microscopy of brain tissue. As expected, Tregs in IL10-/- were unable to make IL-10 in contrast with IL-10-abundant Tregs in the WT mice. Comparison of IL-10-/- to WT mice revealed exacerbated weight loss and 100% mortality in the knockout mice, along with a significant increase in immune cell recruitment to the brain, and a significant increase of inflammatory signaling proteins (IFN-?? and TNF-?) of the effector T cells. We observed enhanced brain pathology, including increased inflammatory infiltrates and neuronal damage and death. Results show that IL-10 plays a vital role in regulating the immune response during CM, protecting the brain from inflammatory damage. This outcome phenocopied our previous findings with mice depleted of Tregs, suggesting that IL-10 is the major anti-inflammatory mechanism employed by Tregs. Moving forward, we aim to confirm that the regulatory T-cells anti-inflammatory function relies on IL-10 production. We plan to transfer IL-10 competent T-cells to the IL-10-/- mice with CM, with expected improvement of their disease outcomes if our hypothesis is correct.
