genomewide characterization of host-pathogen interactions by ...

Maren Depke
Introduction
STUDIES OF HOST-PATHOGEN INTERACTIONS
Different approaches can be applied to define even more and specific interactions between
the host and the pathogen. Besides classical physiological and microbiological methods, the
modern molecular technologies can considerably help to improve the understanding of the
processes acting during encounter of host and pathogen provided that genome sequence
information is available. On the first level, RNA expression profiling will generate an overview on
the potential changes of physiology and metabolism. This approach has the advantage of
monitoring the whole repertoire of the organism using a single analysis method and only one
small sample, because nucleic acid material can be easily amplified by laboratory methods.
Whether such changes of the RNA messenger really will be substantiated by changes on protein
level must be analyzed by global or specific proteomic approaches. Here, different methods
address the diverse cellular fractions and can provide a comprehensive impression of the
different cellular states referring to protein abundance, but also to protein modification and
subcellular protein localization, which is not accessible with the transcriptomic analysis. A
limitation is in some cases the amount of sample material and the bigger effort needed to
perform proteome studies in comparison to transcriptome studies. Results of both studies
complement one another. Hence, a combination of several different approaches in co-operation
studies is strongly recommended.
Model Systems for Studies of Host Reactions Potentially Influencing the
Outcome of Infections
Liver gene expression pattern in a mouse psychological stress model
Psychological and physiological stressors can disturb neuroendocrine, immunological,
behavioral, and metabolic functions (Harris et al. 1998, Leibowitz/Wortley 2004, Mizock 1995)
and adaptive physiological processes aim to reconstitute a dynamic equilibrium (McEwen 2004,
Viswanathan/Dhabhar 2005).
In a murine model of severe, chronic psychological stress due to 4.5 days of intermittent
combined acoustic and restraint stress BALB/c mice developed severe systemic
immunosuppression, neuroendocrinological disturbances and depression-like behavior. Besides
heightened anti-inflammatory cytokine bias, lymphocytopenia, T cell anergy, impaired phagocytic
and oxidative burst responses, increased susceptibility to experimental infection with E. coli,
spontaneous bacterial infiltrations of gut commensals into the lung, reduced clearance of
experimental infections in the long term, attenuation of a hyperinflammatory septic shock, and
finally, behavioral and neuroendocrine alterations and a prominent stress-induced loss of body
mass without significant changes of food and water intake during the observation period became
detectable (Kiank et al. 2006, 2007a, 2007b, 2008).
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