genomewide characterization of host-pathogen interactions by ...

Maren Depke
Discussion and Conclusions
The comparison between the published bacterial supernatant effects and the infection effects
recorded in this study revealed similar functional aspects, although these functions were not
always represented by the same examples. Nevertheless, both studies confirmed each other: 1)
NFκB action (e. g. IL6, JUNB, NR4A2), 2) inflammation (e. g. LIF), 3) inflammatory mediator-related
genes (e. g. PTGS2 alias COX-2). Inflammation-related signal transduction processes were present
with different members of the same families. Moreilhon et al. found induction of JAK1, STAT1,
STAT3 and SOCS2, whereas this study detected induction of JAK2, STAT2 and SOCS1. Similarly,
Moreilhon et al. described induction of pro-inflammatory chemokines/interleukins CXCL1, CXCL2,
CXCL3, CCL20, IL-1α, IL-1β, IL-8, IL-20 and IL-24, and this study found a different set, namely CCL2,
CCL5, CSF1, CXCL10, CXCL11, CXCL16, IL-7, IL-12, IL-15, IL-28, IL-29, and in addition IFNB. From the
group of toll-like receptors, TLR2 was induced in the experiments of Moreilhon et al. while TLR3
was detected with increased expression in the study described in this thesis.
Also cell cycle/apoptosis related genes were found in both studies, but with different
examples. Moreilhon et al. could determine a necrotic phenotype with a transient apoptosis
phase 8 h to 10 h after host-pathogen interaction. In this study, the final fate of the infected cells
was difficult to judge on, because the functional/physiological measurements have not been
performed yet. Here, only an arrest of growth could be postulated from the transcriptome data.
Nevertheless, this is in agreement with proteome result interpretation of Melanie Gutjahr.
Also another study using the cell line MM-39 and washed S. aureus 8325-4 cells from
stationary growth phase (da Silva et al. 2004) describes the epithelial cell reaction as necrotic cell
death after a phase of apoptosis, where a higher concentration of bacterial cells accelerated the
begin of necrosis. Finally, after 24 h a very strong damage of host cells was observed.
Nevertheless, the authors observed that MM-39 host cells were able to defend themselves in the
early phase of infection by the production of SLPI, secretory leukocyte peptidase inhibitor, which
was exhausted in later phases of infection. It has to be mentioned that extracellular bacteria
were not killed in the experiments of da Silva and coworkers and that the strong replication of
non-internalized and host-cell escaped bacteria in the medium during the infection assay and the
parallel production of toxic bacterial products might have influenced the host cells’ reactions
(da Silva et al. 2004). However, transcriptome data of S9 cells during the analysis window of the
study described in this thesis do not allow confirmation of an active defense strategy using SLPI:
SLPI mRNA was expressed, but at a low level, and differential expression was not observed after
infection. Possibly the bronchial epithelial cell line S9 has a different gene expression repertoire
from that of the airway glandular cell line MM-39.
In summary, the in vitro infection study of human bronchial epithelial S9 cells and S. aureus
RN1HG resulted in a picture of a fast, strong proinflammatory reaction of host cells which
revealed central immune response related processes. In agreement with literature reports, the
data led to the conclusion that epithelial cells act as recognition sites for infection and pass this
information to immune cells. Nevertheless, the comparison with other studies revealed that
especially each host cell – bacterial strain combination, but also the additional experimental
settings provoke a specific aspect of host response which supports and necessitates the
extension of research to further of these combinations. Furthermore, the comparison of
proteome and transcriptome results emphasized that the application of both complementing
approaches is recommended and strongly helps to achieve a comprehensive view of hostpathogen
interactions on molecular level.
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