Investigating the role of intestinal IFN-γ expression on barrier immunity during enteric helminth infection

Ridgewell, Olivia Jessica (2025) Investigating the role of intestinal IFN-γ expression on barrier immunity during enteric helminth infection. PhD thesis, University of Glasgow.

Abstract

Enteric helminth infections are a significant global health concern, with over a quarter of the world’s population infected. The infecting parasites often migrate through host tissues and, as large multicellular organisms, they can cause substantial damage. The nematode Heligmosomoides polygyrus bakeri (H. polygyrus) causes a chronic roundworm infection in mice and during early stages of its lifecycle, it enters the intestinal tissue. The main aim of this thesis is to understand the factors that influence the immune responses at this early breach timepoint of infection, with particular interest in the role of IFN-γ production local to the helminth.

Our data show that the early phase of infection is accompanied by barrier disruption and an acute IFN-γ response which precedes the classical Th2 response to helminth infections. Through in vivo neutralisation of IFN-γ, we were able to show that the early production of IFN-γ contributes to increased expression of cell adhesion molecules found in H. polygyrus infection, suggesting a reparative role; and also coordinates and enhances local antimicrobial immunity characterised by increased antimicrobial protein expression and influx of innate myeloid cells to the site of infection.

Enteric helminth infections occur in the context of intestinal microbiota, and in environments where co-infection is frequent. We hypothesised that the antimicrobial responses and epithelial repair responses orchestrated by local IFN-γ could be in response to bacteria potentially invading the ‘breach’ points created by H. polygyrus. Using broad-spectrum antibiotics to eliminate microbiota during H. polygyrus infection, we found that the early IFN γ response is dependent on bacterial presence. Our data suggest that bacterial translocation may not occur, perhaps reflecting the effective antimicrobial and tissue repair responses during the helminth infection. Together our data contribute to our overall understanding of the intestinal environment and immune responses in early H. polygyrus infection. By illustrating a microbiota-driven production of IFN-γ and characterising a role for this cytokine in coordinating local responses, we reveal a potential role for IFN-γ in protecting the host from secondary infection.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Subjects: Q Science > QR Microbiology; Q Science > QR Microbiology > QR180 Immunology
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Supervisor's Name: Milling, Professor Simon and Perona-Wright, Dr. Georgia
• Date of Award: 2025
• Depositing User: Theses Team
• Unique ID: glathesis:2025-85453
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 16 Sep 2025 13:38
• Last Modified: 16 Sep 2025 13:40
• Thesis DOI: 10.5525/gla.thesis.85453
• URI: https://theses.gla.ac.uk/id/eprint/85453

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