Abstract
"African swine fever virus (ASFV) causes a haemorrhagic fever in pigs for which there is no vaccine. ASFV infects macrophages (MΦ) in vivo, a professional antigen-presenting cell (APC) crucial for the adaptive and innate immune response to pathogens. Dendritic cells (DCs) are another professional APC, however their role during ASFV infection is unclear and are a key focus of this project.
The response of lymphocytes and APCs was assessed in vivo in both inbred and outbred animals, highlighting differences in the immune response in inbred animals, indicating a potential influence of the inbred nature of these animals in the development of a protective immune response to ASFV. The frequency and phenotype of DCs was also assessed over time, after in vivo inoculation with attenuated ASFV and challenge with virulent ASFV. Individual DC subsets expressed viral proteins in infected pigs and modulated surface expression of host proteins involved in antigen presentation which may influence the induction of a protective immune response in ASFV infection.
To complement this in vivo approach, the susceptibility of enriched blood DC and monocyte subsets to infection with virulent or attenuated ASFV was tested in vitro. Due to the fragile and rare nature of blood DCs, monocyte-derived DCs (MoDCs), and MΦs (MoMΦs) were assessed as a potential model system to study DC and MΦ interactions with ASFV in vitro. MoDCs were slightly less susceptible to infection with virulent OURT88/1 compared to MoMΦs, while being equally susceptible to attenuated OURT88/3. OURT88/3 infection reduced the phagocytic ability of MoDCs and MoMΦs, while OURT88/1 infection did not, reflecting a potential maturation following OURT88/3 infection. This data demonstrates susceptibility and differential responses of DCs to virulent and attenuated ASFV isolates and support DCs as playing a role in determining protective immunity induced by attenuated ASFV."