Enhancement of Protective Immune Responses in Chickens against Marek's Disease Virus
The work presented in this thesis is an investigation of the use of toll-like receptor (TLR) agonists to induce or enhance immunity in chickens against Marek’s disease virus (MDV). Initially, synthetic double-stranded (ds) RNA, polyriboinosinic polyribocytidylic (poly(I:C)) was administered via different routes to determine the effects of this TLR agonist in chickens. It was demonstrated that administration of poly(I:C) can locally and systemically induce the expression of innate immune response genes depending on the route. To investigate the effects of TLR ligands on enhancing protective efficacy of vaccination against MD, chickens were immunized with a vaccine, herpesvirus of turkeys (HVT), and treated with poly(I:C) and then, infected with a very virulent strain of MDV (RB1B) through the respiratory route. The most reduction in the tumour incidence in vaccinated groups was observed in the birds that had received poly(I:C) treatment twice. These results indicated that poly(I:C) treatment can enhance the efficacy of HVT vaccine and improve protection against MDV. To further explore the role of TLR agonists in inducing immunity against MD, chickens were treated with lipopolysaccharide (LPS) as a TLR4 agonist and CpG oligodeoxynucleotide (ODN) as a TLR21 agonist and infected with the RB1B strain of MDV via the respiratory route. The results of this study indicated that treatment of MDV-infected chickens with TLR4 and 21 agonists induced the expression of type I and II interferons (IFNs) as well as interleukin (IL)-1β and delayed the manifestation of MD clinical signs. Finally, the effects of vaccination with HVT and infection with RB1B MDV were assessed on lung mononuclear cells, given the importance of the respiratory system as the main port of entry for MDV. The findings of this experiment revealed the temporal profile of the expression of cytokines such as IFN-γ, IL-10, and IL-4 by lung mononuclear cells in response to vaccination or infection in the lungs. Overall, the studies presented in this thesis unravel the effects of TLRs in MDV infection and underline the role of TLR ligands in enhancing immunity against MDV.