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PATHOGEN - HOST INTERACTIONS
Coordinators Dr. Juncal Garmendia & Dr. José A. Melero
Respiratory infections: from mechanisms to therapeutics
The main strategy for fighting infectious diseases has focused on targeting enzymes from pathogens with antibiotics . The rapid development of resistance shortens the life span of a therapeutic agent, leading to decreased interest of the industry to develop new agents because the costs are prohibitive compared to the economic potential of the drug . Moreover, there is an urgent need for specific antiviral therapies . Therefore, there is a need to develop effective therapeutics based on new targets/approaches and to develop efficient
prophylactic measures . Importantly, the Spanish Research Plan and the next European research plan, Horizon 2020, consider respiratory infections and development of new therapies as a research priority .
The new project builds on the knowledge generated in the previous Research Programme . It makes a major effort to analyse the transcriptome of alveolar macrophages infected with different pathogens . Analysis of data is currently underway . Interesting results include the induction of antiviral responses by bacteria-infected macrophages and the activation of lipid metabolism in infected macrophages, independently of the pathogen used . These results open new avenues of research to fight infections . Collaborative efforts have also revealed new mechanisms of host-pathogen interaction and similarities between bacterial and viral strategies . Furthermore, the Programme has set up a microarray platform for the study of glycan-pathogen interactions that leads to the identification of some galectins interacting specifically with some pathogens . We also studied the lung surfactant modulation of the inflammatory response in airway epithelial cells infected by respiratory syncytial virus and other pathogens .
The project is divided into 6 work packages . Three of these are meant to pursue ambitious objectives at the forefront of research in infection biology . Importantly, one of these WPs aims to capitalize on the knowledge generated to develop new therapies . Therefore, the first pre-clinical studies have been planned .
ADDED VALUE
Our project focuses on important respiratory pathogens with different infection strategies . We employ an alveolar macrophage cell line as a common denominator in all our investigations, and we focus on common cell targets (pattern recognition receptors-mediated recognition, inflammatory responses, and IFN-induced defence responses) in order to reveal common schemes and principal differences of microbial infection strategies . These studies will allow the design of patient-customized therapeutic treatments . The project provides the required critical mass to carry out the research and developmental activities by joining leading scientists from important institutions in infection biology in Spain . Our work produces synergies based on:
• Distinct but complementary expertise of partners from the disciplines of microbiology, immunology, and cell biology .
• Common use of the established knock-out cells, reagents, and platforms . • Indicator cell lines, tests and developed common reading systems with different pathogens .
The partners will work in a cooperative and supportive way . All WPs are set up in such a way that success is absolutely contingent on close interaction and collaboration .
30 CIBERES » Annual report 2014