FOR 5130:  ImmunoChick- Unravelling the avian immune response in the context of infection

• Subject Area: Agriculture, Forestry and Veterinary Medicine
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 434524639

The chicken has played a pivotal role in advancing biomedical research, significantly contributing to cancer biology, virology, microbiology, and immunology. Beyond its role in research, chickens are among the most important sources of animal protein worldwide. A plethora of pathogens infect chickens and threaten animal welfare, food safety, and public health. To protect the animals from these diseases, chickens receive many vaccines and are considered the most vaccinated species on earth; however, the underlying immune responses remain poorly understood. The ImmunoChick Research Unit aims to advance our understanding of the adaptive immune system in chickens and its interaction with key pathogens. We will achieve this by leveraging our expertise and state-of-the-art technologies developed in the first funding period. These include TCR/BCR repertoire sequencing, MHC tetramers, pathogen-specific MHC peptides, and genetically modified chickens. We use these tools to dissect the roles of B cells, αβ and γδ T cell subsets in responding to important pathogens such as infectious bursal disease virus (IBDV), avian influenza virus (AIV), Marek's disease virus (MDV) and Salmonella spp. We will achieve this in three specific aims. Aim 1 will assess the role of αβ and γδ T cell subsets in the adaptive immunity against important pathogens. Using TCR repertoire analysis, MHC tetramers, and genetically modified chickens lacking specific T cell subpopulations, we will dissect the contributions of these cells to the immune response, immune memory, pathogen clearance, and vaccine-mediated protection. In addition, we aim to identify key γδ T cell ligands and their roles in immune modulation and barrier integrity. Aim 2 focuses on understanding the roles of B cells (and T follicular helper cells, TFH) in immune responses, susceptibility to our pathogens, and vaccine protection in chickens. This includes analyzing B cell development, germinal center dynamics, antibody maturation, and the contribution of TFH cells to B cell function. Aim 3 will assess the role of type I and III interferons in regulating immune responses to MDV and AIV infections and vaccinations using recently generated type I and III interferon receptor knockout chickens. Taken together, this project builds on breakthroughs of the first funding period, is highly collaborative, and uses the complementary expertise of our PIs to tackle critical knowledge gaps and provide important insights into the avian immune system.

• DFG Programme: Research Units
• International Connection: United Kingdom

Projects

• Analyzing Avian T Cell Development and Function during Infection: Insights from Chicken TCR Knockout Models (Applicant von Heyl zu Herrnsheim, Theresa )
• Antigen presentation and memory/plasma cell formation in the chicken’s B cell response (Applicant Härtle, Sonja )
• Assessment of T cell responses against Marek’s disease virus (MDV) infection and vaccination. (Applicant Kaufer, Ph.D., Benedikt Bertold )
• Characterization of regulatory T cells in the chicken (Applicant Kaspers, Bernd )
• Characterization of Tfh cells in germinal centers and antigen-specific T cell responses to infectious bursal disease virus in chickens (Applicant Früh, Ph.D., Simon )
• Comparison and knowledge transfer from human to avian apicomplexan parasites (Applicant Meißner, Markus )
• Contribution of gamma/delta T cells to long-term immunity against Salmonella infection in chickens (Applicant Berndt, Angela )
• Coordination Funds (Applicant Kaufer, Ph.D., Benedikt Bertold )
• Coordination Funds (Applicant Kaufer, Ph.D., Benedikt Bertold )
• Elucidating Chicken γδ T Cell Functions and Ligands via Genetically Engineered Chicken Models (Applicants Kaufman, Jim ;  Schusser, Benjamin )
• Role of T cell subsets in Marek’s disease virus pathogenesis (Applicant Kaufer, Ph.D., Benedikt Bertold )
• Role of γδ T cells in protecting chickens against Salmonella enterica spp. infections (Applicant Berndt, Angela )
• The contribution of the chicken MHC to avian immune responses (Applicant Kaufman, Jim )
• The role of T cells in the protection against epithelial infections in chickens (Applicant Schusser, Benjamin )
• The role of the adaptive immunity in avian influenza virus virulence, pathogenesis, and protection (Applicant Abd El-Whab, El-Sayed Mohammed )
• Towards a better understanding of the antibody response in chickens by characterizing germinal center and antigen-specific B cells (Applicant Härtle, Sonja )
• Understanding the contribution of T cells in infectious bursal disease virus immunopathogenesis and vaccine protection (Applicant Rautenschlein, Ph.D., Silke )
• Understanding the impact of the chicken’s makeup on IBDV pathogenesis – insights form the host perspective (Applicant Rautenschlein, Ph.D., Silke )
• γδ T cell versus NK cell function in intestinal immunity (Applicant Göbel, Thomas )

• Spokesperson: Professor Benedikt Bertold Kaufer, Ph.D.