genomewide characterization of host-pathogen interactions by ...

Maren Depke
Results
Kidney Gene Expression Pattern in an in vivo Infection Model
complement system can cause immense damage also to host cells and tissue. The complement
component C8 consists of three chains (alpha, beta, and gamma) and is the last component in the
C5b-C6-C7-C8 complex that acts as a catalyst in the polymerization of C9 to form the membrane
attack complex MAC. Surprisingly, the gene C8a coding for the alpha chain was repressed in the
infected samples, and also for the gene C8g (gamma chain) a tendency of repression was
recorded. Possibly the opsonization and chemoattractant function of the complement system
was enhanced in infection leading to phagocytosis, while the bacteriolytic function of the
complement system was not potentiated. Otherwise, the components C8 and C9 – produced in
the liver – might be delivered via the blood stream to the site of infection.
Fig. R.2.8:
Complement System
(modified from IPA, www.ingenuity.com).
Colors indicate direction and magnitude of
differential regulation: red – induction; green –
repression. More intense shade of color is used for
higher absolute fold change values. A trend of
induction is shown in yellow. Factor P / Properdin
(CFP) has been inserted manually into the pathway.
As already mentioned, the Toll-like receptor (TLR) signaling cascades lead to the transcription
of different proinflammatory cytokines which themselves activate signaling pathways and the
adequate cellular responses. When using the Canonical Pathways to specifically find infection
relevant signal transduction, the signaling pathways of interferon, IL-6, TREM1, and IL-10
appeared among others with significant p-values.
The pathway “Interferon Signaling” (p = 1.14E−06; ratio = 11/30; Fig. R.2.9) contains the
induced IFN-γ receptor (Ifngr1, Ifngr2) and the IFNα/β-receptor, of which the gene for one of the
two chains (Ifnar2) was induced, too. In the receptor’s signal transduction, the genes for signal
transducers STAT 1 and 2 were induced together with the transcriptionally regulated genes Tap1,
Ifitm1, Irf1, Psmb8, Irf9 and Oas1. Additionally, the inhibitory protein tyrosine phosphatase TC-
PTP (Ptpn2) displayed a trend of induction, probably indicating a counter-regulatory process.
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