genomewide characterization of host-pathogen interactions by ...

Maren Depke
Results
Gene Expression Pattern of Bone-Marrow Derived Macrophages after Interferon-gamma Treatment
Table R.3.9: IFN-γ influence on gene expression of anti-oxidant, detoxification, and lysosomal enzymes and of adhesion molecules in
BMM of BALB/c and C57BL/6 mice.
Rosetta Resolver Annotation fold change a strain
difference
gene
Entrez
description
alias
name
Gene ID
BALB/c C57BL/6 control IFN-γ
Sod2 superoxide dismutase 2, mitochondrial MnSOD 20656 2.1 2.2
Glrx glutaredoxin Grx1, Glrx1, Ttase 93692 2.0 2.2
Gstm1 glutathione S-transferase, mu 1 Gstb1, Gstb-1 14862 -1.9 -1.9
Ctsc cathepsin C DPP1, DPPI 13032 4.0 4.5 x
Ctsh cathepsin H Ctsh 13036 2.2 1.6 x x
Icam1 intercellular adhesion molecule 1 CD54, Ly-47, Icam-1, MALA-2 15894 2.3 2.2
Itgal integrin alpha L Cd11a, LFA-1, Ly-15, Ly-21 16408 2.8 2.0 x
Itgb3 integrin beta 3 CD61, GP3A, INGRB3 16416 -2.3 -2.9
Itgb7 integrin beta 7 Ly69 16421 2.5 2.1
Pcdh7 protocadherin 7 54216 1.7 1.7 x
Vcam1 vascular cell adhesion molecule 1 CD106, Vcam-1 22329 3.1 1.7
a Fold change values were calculated from expression intensities of IFN-γ treated BMM in comparison to control BMM from the mean
of three biological replicates. Differential expression in statistical testing with p* < 0.01 and a minimal absolute fold change of 1.5 is
indicated in bold.
Biological context of gene expression differences between BALB/c BMM and C57BL/6 BMM
Comparison of differentially expressed gene lists (Fig. R.3.3 A) and comparison of log 2 -ratio
data (Fig. R.3.3 B) revealed highly similar strain differences between BALB/c and C57BL/6 BMM at
both treatment levels, non-treated medium control and after IFN-γ treatment, even for genes
which were differentially expressed only in one of the two comparisons. Therefore, the biological
context of strain differences was further analyzed using the union set of differences at control
level and after IFN-γ treatment.
First, the list of in total 324 genes, which exhibited differences between the strains in at least
one of the two treatment conditions, was subjected to a global functional analysis using
Ingenuity Pathway Analysis (IPA, www.ingenuity.com), which compared functional categories
within the data set with those of the complete array and assigned a p-value to rate on significant
overrepresentation (Table R.3.10).
This analysis revealed on the one hand categories with immune response related functions
like “Inflammatory Response”, “Antigen Presentation”, and “Immune Cell Trafficking”, which was
not surprising because the gene expression repertoire of BMM independent from the strain of
which the cells were derived is focused at the immune response as the proprietary function of
the BMM. Metabolic functions and the category “Cell Death” additionally appeared in the
analysis of strain differences.
Also for the strain difference aspect of this study, IPA’s canonical pathway analysis was
applied for a more detailed view (Table R.3.11).
Here, the pathway “Complement System” appeared with the highest ratio value. Four genes
differentially expressed between the strains were included in this pathway. Noticeably, the ratio
values for this and further pathways were lower than in the analysis of IFN-γ effects on BMM.
This might reflect the smaller number of genes exhibiting differences between the strains in
comparison to the number of genes which are influenced by IFN-γ, but also the possibility that
the strain differences are more distributed among the pathways and functions.
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