Genetically Engineered Chickens as Tools to Study Interferon Functions in Immunity

• Applicant: Dr. Mohanned Alhussien
• Subject Area: Animal Breeding, Animal Nutrition, Animal Husbandry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 567651016

This project aims to uncover the immunobiology and functional roles of type I and type III interferons (IFNs) in chickens. IFNs are key immune proteins that help combat infections, but their precise roles and interactions in chickens remain poorly understood. This study will investigate how these IFNs regulate immune responses and contribute to host defense against infections using genetically modified chicken lines lacking receptors for type I IFN, type III IFN, or both. To achieve this, a series of in vitro, in ovo, and in vivo experiments will be conducted to analyze IFN-mediated immune mechanisms under both physiological and infectious conditions. The study is structured around three key objectives: 1. Unravel the distinct and overlapping signaling pathways of type I and III IFNs, their associated interferon-stimulated genes (ISGs), and their role in cellular and mucosal immunity under pathogen-free conditions. Recombinant IFNs will be used to identify ISGs regulated by each IFN type across different tissues. Additionally, the activation of IFN pathways by toll-like receptor (TLR) will be unraveled using TLR agonists. This will provide a comprehensive understanding of how IFNs are induced and function under physiological conditions. 2. To study the IFN defense mechanism against viral infections. This objective will examine how type I and III IFNs shape immune responses against viral infections, specifically Newcastle Disease Virus (NDV) and Influenza A virus (H1N1). This will help clarify the distinct roles of type I and III IFNs in antiviral defense and their impact on susceptibility to infection and disease progression. 3. To investigate the IFN defense mechanisms against bacterial infections. Type I and III IFNs play a crucial role in Salmonella pathogenesis by influencing immune responses and intestinal barrier integrity. Using both in vitro and in vivo models, this objective will explore how IFNs affect Salmonella invasion, persistence, and spread within the host. This research will advance our understanding of IFN-driven immunity in chickens and how pathogens manipulate IFN signaling to evade it. Given the economic and public health impact of viral and bacterial diseases in poultry, these findings will support the development of more effective vaccines and disease control strategies. With zoonotic risks like Salmonella and influenza, this study has broader implications for food safety and global health initiatives. By enhancing disease resistance, this research aligns with One Health principles, promotes sustainable poultry production, and contributes to reducing antibiotic use, economic losses, and zoonotic disease transmission.

• DFG Programme: Emmy Noether Independent Junior Research Groups