Elina Välimäki

University of Helsinki
Supervisor: Tuula Nyman
Funding: ISB
Date: 2012-01-01

Activation of innate immunity by pathogens and endogenous danger signals

Activation of innate immune system is the first response to microbial infection and tissue damage. Pathogens or tissue breakdown are detected by pattern recognition receptors (PRRs) expressed in innate immune cells, including macrophages and dendritic cells, and in the epithelial cells of skin and mucosa. PRRs recognize molecular motifs common to pathogens, also called pathogen associated molecular patterns. They also recognize endogenous molecules if encountered in incorrect compartments implying that the structure of the cells has been damaged. These are called danger- or damage-associated molecular patterns. Activation of innate immunity results in inflammation aiming to pathogen elimination, tissue repair and activation of adaptive immune system responses. Innate immunity is an essential arm of immune defence system, and recent findings support its role also in the development and maintenance of inflammatory and autoimmune diseases.

The objective of this project is to characterize the innate immune responses that detection of pathogen and danger signals activate by combining traditional molecular and cellular biology techniques with modern proteomics and bioinformatics tools. We will study the pathways activated by recognition of viral double-stranded RNA in human epithelial cells, as well as the pathways activated by danger signals ATP and monosodium urate in human macrophages. This project is important in providing information that enables understanding the course of innate immune responses, and also immune-mediated diseases.