Work Package 1
Understanding the impact of the chicken’s makeup on IBDV pathogenesis – insights form the host perspective
Infectious bursal disease virus (IBDV) is one of the most important immunosuppressive chicken pathogens worldwide. Despite vigorous vaccination, IBDV field outbreaks occur. Overall, the influence of host traits on disease development and protective immunity is poorly understood in avian species.
For IBDV infection it was shown that genotype and age impact innate and acquired immunity, but the mechanisms behind that remain largely uncharacterized. Older studies suggest that the availability of target cells, especially B cells as the main cellular target for IBDV, may affect the outcome of the infection as bursectomy abrogates clinical disease. While humoral immunity is very important for IBDV protection, T cells are also suggested to play a significant role in virus control and recovery from bursa lesions. Our recent investigations comparing wild-type (WT) and γδ T cell knockout (KO) chickens after IBDV-infection indicated that γδ T cells do not play a major role in IBDV pathogenesis, in contrast compensating αβ T cell populations seem to facilitate faster virus clearance and recovery of the bursa of Fabricius. Cytokine-expression analysis suggested a role for regulatory and cytotoxic T cells in this process. We hypothesize that the genotype and age of chickens contribute to the availability of IBDV-target cells. Variations in these different indicated traits may affect virus pathogenesis and immune responses. We will use four chicken genotypes (aim 1) or four age groups of a selected line (aim 2) to investigate the cell composition of target tissues and compare the distribution of IBDV-infected cells, lesion development and recovery after inoculation with very virulent, virulent or intermediate plus IBDV strains.
In addition, we will characterize host-associated variations in B and T cell immunity by looking at the composition of these cells in the circulation and locally in target tissue, the B (aim 1 and 2) and T (aim 1) cell receptor bulk repertoire, and the development of the humoral immune response after IBDV inoculation. We will compare IBDV infection between WT and B cell heavy chain KO (JH-/-) chickens to analyze pathogenesis in the in the absence of classical IBDV target cells and the humoral immune response. Adoptive transfer of IBDV-primed splenic T cell subsets will make it possible to determine T cell immunity in protection in intact and a B cell deficient host. We will use the B cell KO chicken model also to characterize non-B cell target cells more closely, in order to understand their contribution to immunosuppression and disease development. Overall, our studies will help to improve prophylactic strategies
against IBDV by taking into consideration possible variations in the chicken’s makeup and the impact on IBDV pathogenesis and immune response. We will therefore contribute to the overall improvement of chicken health and welfare, and in addition may inform development of new farm animal vaccination strategies.
Principl investigator:
Prof. Dr. Silke Rautenschlein, PhD