Maia Lintner
Pronouns: she/her
Research Mentor(s): Michal Olszewski
Research Mentor School/College/Department: Internal Medicine, Pulmonary and Critical Care Medicine / Medicine
Program:
Authors: Maia Lintner, Rylan Hissong, Kristie Goughenour, Jintao Xu, Michal Olszewski
Session: Session 4: 1:40 pm – 2:30 pm
Poster: 57
Abstract
Cryptococcus neoformans (C. neo) is an environmental fungal pathogen that results in severe infections in immunocompromised individuals. Cryptococcal meningoencephalitis (CM), the most severe and life-threatening form of C. neo infection, kills more than 100,000 people each year (Rajasingham et al., 2022). Although an immune response is needed for clearance of C. neo, its pathology is often driven by a host-damaging immune response, worsening neurological symptoms and mortality. Regulatory T-cells (Tregs) are a population of T cells that mark the beginning of the resolution of the central nervous system (CNS) inflammatory response, presumably suppressing the harmful CM component, and express chemokine receptor-8 (CCR8), whose role in the CM is unknown (Neal et al., 2017). This research explores the role of CCR8 in the recruitment of Tregs into the C.neo-infected brain and its importance in reducing pathological inflammation in CM. Six C57BL/6 mice were infected intravenously with C. neo strain 52D, with three CCR8-depleted mice and three control mice. Mice in the CCR8-depleted group were treated with an anti-CCR8 antibody. At day 21, these mice were euthanized and their brains were harvested and visualized with immunofluorescence staining, indicating the localization of Tregs and CCR8 in the infected brain. The data shows that neutralizing CCR8 with antibodies reduces CNS Treg numbers and increases inflammation with CM. Therefore, CCR8 signaling is important for recruiting Tregs and controlling inflammation. The findings from this research advance our knowledge of host response mechanisms and may help mitigate inflammatory brain injury in pCM patients.
