genomewide characterization of host-pathogen interactions by ...

Maren Depke
Introduction
with heightened release of glucocorticoids. Prolonged and increased release of catecholamines is
associated with cardiovascular diseases such as hypertension, myocardial infarction, or stroke.
Excessive secretion of glucocorticoids was linked to diabetes, dyslipidemia, cardiovascular
alterations, immunosuppression, and mood disorders (Lundberg 2005, McEwen 2004,
Viswanathan/Dhabhar 2005, Wrona 2006).
Recently, Kiank et al. described that BALB/c mice developed severe systemic immune
suppression, neuroendocrinological disturbances and depression-like behavior due to 4.5 days of
intermittent combined acoustic and restraint stress which serves as a murine model of severe,
chronic psychological stress (Kiank et al. 2006, 2007a). Immunosuppression was substantiated by
a heightened anti-inflammatory cytokine bias, an apoptotic loss of lymphocytes leading to
lymphocytopenia, T cell anergy, and impaired phagocytic and oxidative burst responses. The
immunodeficient state increased the animals’ susceptibility to experimental infection with E. coli
(Kiank et al. 2006, 2007b). Repeatedly stressed mice actually developed spontaneous bacterial
infiltrations into the lung measurable even 7 days after the last chronic stress cycle, which was
associated with a reduced inducibility of IFN-γ, a cytokine that was shown to be important to
prevent spreading of translocated commensals from the gut (Kiank et al. 2008). On the one hand,
stress-induced immunosuppression was accompanied with a reduced clearance of experimental
infections in the long term, but on the other hand, with attenuation of a hyperinflammatory
septic shock (Kiank et al. 2006, 2007a). Furthermore, behavioral alterations with increased
depression-like behavior and neuroendocrine alterations such as prolonged activation of the HPA
axis and increased turnover of catecholamines were documented.
Finally, 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). It is known
that stress exposure is linked to changes of body weight. There is evidence that hypothalamic
control of food intake is influenced by stress, which in consequence alters metabolism. In such a
situation, some people lose and others gain weight in response. However, the molecular
mechanisms of the stress to body weight connection remain to be elucidated.
It is important for the understanding of stress-induced immunoregulatory mechanisms that
stress hormones like catecholamines and glucocorticoids can modulate several liver functions
including carbohydrate, protein and lipid metabolism or affect the immune response. Especially
corticosteroids can suppress inflammatory processes by preventing the release of
proinflammatory mediators, by diminishing immune cell trafficking, phagocytosis and radical
production or by down-regulating antigen presentation, by inhibiting lymphocyte proliferation,
and by inducing apoptosis of immune cells. Thus, prolonged increase of glucocorticoid levels
during chronic stress can activate hepatic catabolic pathways but also effectively suppress the
local immune response (Bartolomucci 2007, Chida et al. 2006, Elenkov 2004, Swain 2000).
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