Unravelling the role of B cells in mediating the immune response and providing protection against Salmonella infection using gene-edited chickens

• Applicant: Mohanned Alhussien, Ph.D.
• Subject Area: Veterinary Medical Science
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 499362301

Chickens are one of the major sources of animal-derived protein in human diet. However, they are regularly exposed to various pathogens which threaten their welfare and cause huge economic losses to the poultry industries. Moreover, some pathogens, such as Salmonella, are transmittable to humans and can cause the death of lots of people every year. Out of 2,600 Salmonella serotypes, Salmonella Enteritidis (S. Enteritidis) is the most common serotype associated with human illness in most countries. Current vaccination strategies are far from being sufficient to manage and control this disease in poultry. Therefore, there is growing interest to develop immune modulation based effective vaccination strategies for this public health problem. B lymphocytes secrete antibodies specific for each invading pathogen and this is critical for the development of effective vaccination strategies capable of providing protection against various diseases. The role of B cells in the defense mechanism against Salmonella is a long-standing matter of debate. This is attributed to the traditional inefficient methods employed to produce B cells deficient chickens, and their physiological side effects. Genetically modified animals have always been extremely useful tools to study the role of specific molecules. The main objective of this proposal is to unravel the role of B lymphocytes in the pathogenesis of Salmonella Enteritidis using genetically modified chickens. In the first aim, B cells knockout chickens, deficient of antibodies, will be utilized to explore the role of B cells in the pathogenesis of Salmonella and in mediating the protective effects of live vaccine currently used to control Salmonella in poultry. This aim will uncover the underlying mechanism by which B cells respond to Salmonella infection and control the functional and transcriptomic activities of heterophils which are critical for the host defense mechanism against Salmonella. This will help to develop immune-modulation strategies and more effective vaccines against Salmonella infection in chickens. In the second aim, I will investigate the likelihood of restoring the immune response in B cells deficient chickens using in vivo adoptive transfer of splenic and bone marrow B cells from mCherry expressing chickens. Identifying the immunological characteristics of B cells based on their source will make it possible to modulate and control their functions precisely. Ultimately, this project will improve the health and welfare of chickens and humans, and prevent huge economic losses associated with this public health problem.

• DFG Programme: WBP Position