Page 36 - MemoriaES-Eng

RESEARCH PROGRAMMES

differences of microbial infection strategies. These studies will allow the design of

patient-customized therapeutic treatments. The project provides the required criti-
cal 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.

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.

In order to better understand how pathogens stimulate, inhibit, and manipulate host
Aims and
cell functions, we will analyse bacteria (K. pneumoniae, Haemophilus influenzae no
objectives
tipable, S. pneumoniae, M. tuberculosis, S. aureus) and viruses (Influenza A viruses,

paramyxoviruses, and respiratory syncytial virus) specified by various infection strate-
gies. Analysis of pathways targeted by pathogens may reveal the strategies used to

subvert immune responses and lead to the identification of the various Achil-

les heels of host defence. Although the immunomodulatory mechanisms used by
viruses and bacteria may appear to be quite different, pathogens have to overcome

the same host immune defences. Hence it is not surprising that there may be shared

mechanisms. Consequently, the identification of a central core of systems implicated
in host defence against several pathogens, which could be targeted for therapeutic

manipulation, is an important goal of this project.

Our main hypothesis is that there is a common host response to infections associated
with the clearance of the pathogen. In turn, pathogens try to counteract this response

using conceptually similar but physically distinct processes. On the other hand, differ-

ent signals (mediated by innate immune molecules and/or drugs) can tip the balance
of this response, thereby affecting the outcome of the host-pathogen interaction.

The main objectives of our Programme are:

1. To identify anti-immune strategies of different pathogens, focusing on their

ability to modulate gene expression and hence cellular function via the ma-
nipulation of innate immune response.

2. To analyse the activation of pattern recognition receptors upon infection
with emphasis on these receptors launching IFN-dependent responses and control- 13
20
ling viral infections.
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3. To identify a set of IFN-dependent anti-infection determinants that might PO
E
be common to viruses and bacteria.
L R
A
4. To evaluate the impact of molecules of the innate immune system (galectins NU
and surfactant) on host-pathogen interactions.
N
A
5. To uncover strategies to avoid intracellular killing.
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