Work package 1: Analysis of innate (early) cellular responses and signalling events
Projects will focus on the ability of the pathogens to modulate the activation of key signalling pathways, NF-κB, MAPKs and IRFs, leading to altered gene expression and thus modulation of cellular functions in response to bacteria and helminths infections. Emphasis will be placed on analyzing the activation of host receptors sensing infections and the activation of inflammatory responses mainly focusing on production of type I IFNs. Focus will be placed on identifying bacterial means to subvert type I IFN production and on comparing the strategies discovered with those displayed by viruses.These joint efforts should lead to the identification of a set of IFN-dependent anti-infection determinants which might be common to viruses and bacteria. Finally, efforts will be devoted to identify new pathways of immunomodulation to generate immune protection avoiding tissue damage and systemic effects.
Work package 2: Identification of cellular factors (and mechanisms) and pathogen determinants involved in pathogen replication
Projects aim to identify the strategies employed by different pathogens to counteract the microbicidal activity of soluble innate molecules and, on the other hand, to avoid intracellular killing. Emphasis will be placed on the antimicrobial action of type I IFNs. Three innovative projects will be devoted to explore new strategies to manipulate immune responses by targeting receptors sensing infections, and cellular pathways subverted by pathogens.