Expression and activity of intracellular pattern recognition receptors in dendritic cell subsets and their role in anti-viral immunity

Academic head of project management: Rajnavölgyi Éva

• Title of project: Sejten belüli mintázatfelismerő receptorok kifejeződése és aktivitása dendritikus sejt altípusokban és szerepük a vírusellenes immunitásban
• Type of grant: OTKA-NK
• Description: Dendritic cells (DCs) are key regulators of immune responses. Acting as sentinels they sense pathogens and their microbial products through conserved pattern recognition receptors (PRRs). Upon recognition, pathogens are internalized and the processed antigens are presented to antigen-specific T-cells. Recent advances in DC-biology revealed that the term dendritic cell covers a heterogenous cell population with distinct characteristics and specialized functions. The goal of this project is to study the signalling cascades initiated by intracellular viral sensors of the RIG-, Toll- and NOD-like families in human monocyte-derived DC subsets (moDC). Distribution, activity and the functional interplay between these pathways will be analyzed by eliminating individual or multiple members of the signaling pathways using RNA interference. The pathways will be analysed to the level of direct interaction, positive and negative regulators, mitochondrial generation of reactive oxigen species and in the CD1a-positive and CD1a-negative subsets and in plasmacytoid DCs. In addition, the recently emerging type I interferon, IFNλ will be evaluated as a potential link between DC subtypes in coordinating anti-viral responses. These experiments will shed light on new pathways induced by host-microbe interactions and have a great impact on designing and developing PRR-based preventive vaccines and immunomodulatory treatments against viruses and tumors.
• The duration of the project: January 1, 2012 – March 31, 2015
• Actual total costs: 68.823.000 (HUF)
• Type of research: Basic