51³Ô¹Ï

Topic

Investigating the function of eosinophils in mucosal immunity

Department of Biochemistry and Microbiology

Date & location

• Tuesday, May 27, 2025
• 10:00 A.M.
• Engineering & Computer Science Building
• Room 128

Examining Committee

Supervisory Committee

• Dr. Lisa Reynolds, Department of Biochemistry and Microbiology, 51³Ô¹Ï (Supervisor)
• Dr. Brad Nelson, Department of Biochemistry and Microbiology, UVic (Member)
• Dr. Julian Lum, Department of Biochemistry and Microbiology, UVic (Member)
• Dr. Robert Chow, Department of Biology, UVic (Outside Member)

External Examiner

• Dr. Alberto Caminero, Department of Medicine, McMaster University

Chair of Oral Examination

• Dr. Steve Perlman, Department of Biology, UVic

Abstract

Eosinophils are a highly abundant immune cell type in the gastrointestinal (GI) tract at steady-state, where they have recently been reported to contribute to tissue homeostasis in response to nutrient and bacterial microbiota-derived signals. Eosinophils are also elevated in the GI tract of some individuals with inflammatory bowel disease (IBD) who are also more susceptible to enteric bacterial infections. Further, therapies to treat hypereosinophilic syndromes have been designed to deplete eosinophils from the human body rendering some people completely devoid of this cell type. Together, these observations emphasize the need to gain a deeper understanding of the role of eosinophils in the GI mucosa.

In this thesis, I examine the function of eosinophils under three different contexts within the murine intestinal tract: 1) steady-state secretory immunoglobulin A (sIgA) production, 2) enteric bacterial infection, and 3) the development of oral tolerance. We find that contrary to previous reports, eosinophils are not essential for the maintenance of sIgA in the GI tract at steady-state. Instead, our findings emphasize the importance of optimally controlling rearing and housing conditions throughout life between mice of different genotypes when their phenotypes are being assessed. Further, we determine that eosinophils are responsive to an enteric infection with the bacterial pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) but not essential for controlling S. Typhimurium colonization within the GI tract. Finally, we established a mouse model to investigate the contribution of eosinophils to oral tolerance development in early life. Using this model, we uncover immune responses to dietary antigens unique to the early life period and determine that eosinophils are not an essential cell type contributing to oral tolerance in early life.

Collectively, these results contribute to our understanding of eosinophils within the GI mucosa, which ultimately will help inform treatment strategies for people living with elevated or depleted levels of eosinophils. Further, our findings lay the groundwork for future well-controlled and robust studies of eosinophils as well as oral tolerance development during the early life period.