Immunomodulatory peptides as novel anti-infectives
The aim of this project was to identify trained immunity-associated biomarkers in human, mouse, porcine and bovine immune cells to facilitate development of novel veterinary pharmaceuticals by Zoetis that enable reduction of antibiotic use in production animals.
In chicken and mouse models, derivatives of chicken cathelicidin-2, a small peptide with antimicrobial and immune cell modulating properties have been shown to establish partial protection against bacterial infections which may be explained by “trained immunity”. These derivatives are in development as alternatives for antibiotics in production animals in cooperation with veterinary pharmaceutical company Zoetis.
Sustainable and safe alternative strategies to prevent or fight infections in animals are urgently needed to reduce the use of antibiotics in livestock. Few novel antibiotics are in development and new antimicrobials are also at risk of rapidly generating antimicrobial resistance.
Transcriptome (RNA-seq) analysis of mouse bone marrow-derived immune cells and a human macrophage cell line revealed similar changes in biological processes, such as cell metabolism, that are associated with the response to stimuli. In part these processes overlap with those observed in β-glucan-mediated human macrophage training. Together this will enable to identify potential biomarkers for trained immunity. Identified biomarkers will aid in the development of trained immunity-based strategies to improve human and animal health.
