Project

Optimized activation of plasmacytoid dendritic cells to increase Th1 responses in the pig

Code
1SH0Q24N
Duration
01 November 2023 → 31 October 2027
Funding
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Virology
  • Agricultural and food sciences
    • Veterinary immunology
    • Veterinary microbiology
Keywords
Th1 response alphaherpesviruses plasmacytoid dendritic cell
 
Project description

The adaptive immune response is of key importance in many strategies to prevent or suppress disease in man and animal, including vaccination and immunotherapy. Importantly, a specific type of adaptive response, a Th1 response, is often crucial to interfere with virus infection and cancer progression. Plasmacytoid dendritic cells (pDC) are innate immune cells that, upon activation, produce massive amounts of cytokines (particularly type I interferon, but also IL-12 and TNF) and are thereby strong drivers of a Th1 response in man as well as in pig. Hence, strategies to trigger pDC activation hold great promise for prophylactic/therapeutic settings that benefit from a Th1 response. Recent data of our lab, including crucial data from the candidate, revealed two exciting ways to trigger strong pDC activation. (i) We generated in-house cell culture-adapted strains of the porcine alphaherpesvirus pseudorabies virus that trigger strongly increased pDC activation, putting us in a unique position to discover the viral and host factors that trigger this pDC hyperactivation. (ii) We found that treatment with cGAMP primes porcine pDC for strongly enhanced activation. The aim of the current PhD application is to unravel the mechanisms underlying and consequences of these modes of pDC activation and to correlate them with Th1 responses in the pig, thereby generating a crucial groundwork to develop tools and strategies to trigger pDC activation for prophylactic/therapeutic purposes.