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Host-Pathogen Interaction

RESPIRATORY INFECTIONS: FROM MECHANISMS TO
Coordinators
THERAPEUTICS
Dr. Juncal Garmendia &

Dr. Jos A. Melero
The main strategy for fighting infectious diseases has focused on targeting en-
zymes 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, Ho-

rizon 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 alveo-

lar macrophages infected with different pathogens. Analysis of data is cur-
rently 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 av-

enues 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, 13
20
one of these WPs aims to capitalize on the knowledge generated to develop new T
OR
therapies. Therefore, the first pre-clinical studies have been planned.
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Added value
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Our project focuses on important respiratory pathogens with different E
infection strategies. We employ an alveolar macrophage cell line as a common ER
B
denominator in all our investigations, and we focus on common cell targets (pat- CI
tern recognition receptors-mediated recognition, inflammatory responses, and

IFN-induced defence responses) in order to reveal common schemes and principal
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