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oai:figshare.com:article/32633493 2026-10-01T17:02:43Z portal_1172 item_type_8 month_year_10_2026

Defining the mechanisms and therapeutic potential of Helminth-derived Immunomodulatory Peptides Sinead Ryan (12612865) PUREID: 379175209 FhHDM-1 immunomodulatory lung infection lung injury macrophage Helminth effector molecules present within excretory-secretory protein fractions have been viewed as potential therapeutics for atopic and inflammatory disease due to their immunomodulatory capabilities. The discovery of helminth defence molecules (HDMs) represented a family of proteins with distinctive features analogous to cathelicidins. The Fasciola hepatica HDM (FhHDM-1) significantly modulates macrophage function and has regulates inflammation in several preclinical models of allergic and autoimmune disease. This thesis has provided further insight into the role of FhHDM-1 in inflammation in vitro and in vivo. We have also revealed the potential of FhHDM-1.C2, a 40mer C-terminal derivative of the FhHDM-1 sequence, as a potential therapeutic in our model of acute lung injury with comparable effects to the native sequence peptide. Our studies conclude that FhHDM-1 targets AMPK signalling in macrophages and in lung tissue during inflammation. In an in vivo model of pulmonary Pseudomonas aeruginosa infection, we found FhHDM-1 mediated the recruitment of phagocytic cells which was accompanied by increased bacterial clearance in the lung although FhHDM-1.C2 only partially replicated these effects. We propose that FhHDM-1 is a critical mediator of anti-microbial responses in the lung and has potential as a therapeutic for acute infection. This is due, in part, to increased AMPK signalling in macrophages, and potentially other cells, which enhances anti-microbial activity in the mouse lung. Our studies also highlight avenues for further research using the FhHDM-1.C2 peptide which elicits similar effects but clearly these effects are dependent on a range of factors such as concentration of peptide. Thesis embargoed until 31st December 2027 2026-10-01T17:02:43Z Text Thesis 10.17034/32633493.v1 https://figshare.com/articles/thesis/Defining_the_mechanisms_and_therapeutic_potential_of_Helminth-derived_Immunomodulatory_Peptides/32633493 All Rights Reserved Open Access after 2027-12-31