genomewide characterization of host-pathogen interactions by ...

infection rate
cfu / organ
Maren Depke
Introduction
Kidney gene expression pattern in an in vivo infection model
S. aureus can be transmitted to the blood after body injury or by medical devices like
catheters. An elementary model to mimic blood stream infection is the intra-venous infection of
laboratory animals, e. g. mice. Host reactions can be monitored by physiological, immunological
or molecular readout systems. In this study, transcriptome analysis was applied.
Strongest accumulation of S. aureus after i. v. infection of mice is observed in kidneys, which is
also accompanied by bacterial proliferation in the time course of infection (Fig. I.7, data courtesy
of Tina Schäfer). Thus, this organ was chosen for host gene expression profiling.
Fig. I.7:
Accumulation and bacterial proliferation of S. aureus
Xen29 in murine kidney tissue after i. v. infection.
Female BALB/c mice were infected with 1.0E+08 cfu
via the tail vein. Data represent median and
interquartile range of n = 3 experiments.
Data courtesy of Tina Schäfer, Würzburg.
1.0E+09
1.0E+08
1.0E+07
1.0E+06
1.0E+05
1.0E+04
1.0E+03
1.0E+02
1.0E+01
0.25 24 48 72
time post infection / h
Although the virulence of sigB deficient strains is often reported to be similar to that of wild
type strains the pathogenesis or pathomechanism of infection might be different. Therefore, the
rationale of this study was to investigate whether the deletion of sigB will lead to a different
reaction of the infected host.
Host cell and pathogen gene expression pattern in an in vitro infection model
While S. aureus colonizes humans in the anterior nares, it can be cause of pneumonia when
transferred to the lung e. g. by aspiration or medical devices. In a longitudinal study with more
than 10000 patients in Japan, S. aureus was identified as one of the leading causative organisms
of pneumonia besides Streptococcus pneumonia and Haemophilus influenzae (Goto et al. 2009).
Here, different cell types first encounter the pathogen: Cells associated with structural and
functional aspects of lung and “guardian” cells of the immune system, e. g. alveolar macrophages.
Epithelial cells form the inner surface of the lung. Cilial epithelial cells transport mucus out of the
organ. The mucus is produced in the lower bronchia and alveoli by type II pneumocytes and
functions as surfactant to reduce surface tension and as protective film to remove inhaled
particles and pathogens. Adjacent type I pneumocytes take part in oxygen exchange of the air
with the blood.
A model to study reactions of epithelial cells to pathogens is the human bronchial epithelial
cell line S9. S9 cells originate from the IB3-1 cell line, which was established about 20 years ago
from a male, white cystic fibrosis (CF) patient’s bronchial epithelial cells after transformation with
adeno-12-SV40 virus (Zeitlin et al. 1991). This cell line contains the non-functional chloride
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