Advisor(s)
Casey Weaver
Committee Member(s)
Charles Elson
Gregory Payne
Hui Hu
Laurie Harrington
Robin Hatton
School
Joint Health Sciences (Interdisciplinary)
Document Type
Dissertation
Department (new version)
Pathology
Date of Award
9-11-2025
Abstract
The intestinal epithelium maintains a complex relationship with both commensal microbiota and enteric pathogens while orchestrating local immune responses. Although intestinal epithelial cells (IECs) can express MHC class II molecules during inflammation, their functional contribution to pathogen-specific adaptive immunity and immunological memory remains poorly defined. This dissertation investigates the hypothesis that IECs actively shape CD4+ T cell responses through antigen presentation, using Citrobacter rodentium infection as a physiologically relevant model of human attaching and effacing bacterial pathogens. The C. rodentium model offers unique advantages for dissecting epithelial-immune interactions: it naturally infects mice through oral inoculation, exhibits precise anatomical tropism for the distal colon, and employs a type III secretion system to inject effector proteins directly into host cells. While IL-22 signaling is known to be essential for surviving infection and tissue-resident memory T cells develop following bacterial clearance, fundamental questions remain about how epithelial cells communicate with T cells during infection and memory formation. The mechanisms determining whether bacterial antigens generate tissue-resident versus systemic immunity are particularly unclear. This dissertation employs an integrated approach combining large-scale single-cell transcriptomics, engineered bacterial strains expressing model antigens in distinct subcellular compartments, and novel proximity-labeling techniques to interrogate IEC-T cell interactions across the infection timeline. By examining how antigen localization influences T cell differentiation and investigating the requirements for epithelial MHCII in memory T cell maintenance, this work addresses longstanding questions about mucosal immunity. The findings have broad implications for understanding inflammatory bowel disease pathogenesis, where dysregulated epithelial-immune interactions may perpetuate inflammation, and for rational mucosal vaccine design, where harnessing epithelial antigen presentation pathways could enhance protective immunity at barrier surfaces.
ProQuest ID
Recommended Citation
Wilson, Christopher Garrett, "Compartmentalized Antigen Presentation By Intestinal Epithelial Cells Directs Cd4 T Cell Fate" (2025). All ETDs from UAB. 7391.
https://digitalcommons.library.uab.edu/etd-collection/7391
