genomewide characterization of host-pathogen interactions by ...

Maren Depke
Results
Gene Expression Pattern of Bone-Marrow Derived Macrophages after Interferon-gamma Treatment
endoperoxide synthase 2 (Ptgs2), coding for the enzyme responsible for prostaglandin E 2
biosynthesis, was induced as well as different 2'-5'-oligoadenylate synthetase genes (Oas2, Oas3,
Oasl1, Oasl2). They are part of the innate immune response. Serum amyloid proteins are part of
the acute phase response. In humans, Saa genes are known to be expressed not only in the liver,
but also in activated monocytes/macrophages (Urieli-Shoval et al. 1994). In this study, serum
amyloid A 3 (Saa3) was induced in murine BMM after IFN-γ treatment.
BMM induced plasma membrane receptors after treatment with IFN-γ. Among others, the
induction of IgG Fc receptor with high affinity I and with low affinity IV (Fcgr1 and Fcgr4), of tolllike
receptors 2, 9, and 12 (Tlr2, Tlr9, Tlr12), and of co-stimulatory receptors Cd40 and Cd86 was
observed. Additionally, CD274 (B7-H1, PD-L1), ligand for the immunoinhibitory receptor PD-1 on
activated B and T cells, and the second PD-1 receptor, programmed cell death 1 ligand 2
(Pdcd1lg2; PD-L2) exhibited induction (Table R.3.8).
Table R.3.8: IFN-γ influence on expression of immune function related genes 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
Nos2 nitric oxide synthase 2, inducible iNOS,Nos2a 18126 18.6 25.5
Kynu kynureninase (L-kynurenine hydrolase) 70789 4.0 5.2
Wars tryptophanyl-tRNA synthetase WRS 22375 3.7 4.4
Ptgs2 prostaglandin-endoperoxide synthase 2
COX2, PHS-2, Pghs2,
TIS10, PGHS-2
19225 16.2 15.4
Oas2 2'-5' oligoadenylate synthetase 2 Oasl11 246728 2.3 2.4 x
Oas3 2'-5' oligoadenylate synthetase 3 Oasl10 246727 3.0 4.4
Oasl1 2'-5' oligoadenylate synthetase-like 1 oasl9 231655 4.8 2.4 x x
Oasl2 2'-5' oligoadenylate synthetase-like 2
Oasl, M1204, Mmu-
OASL
23962 2.6 4.2
Saa3 serum amyloid A 3 l7R3, Saa-3 20210 3.8 5.7
Fcgr1 Fc receptor, IgG, high affinity I
CD64, IGGHAFC,
FcgammaRI
14129 4.6 4.9 x
Fcgr4 Fc receptor, IgG, low affinity IV
Fcrl3, CD16-2, FcgRIV,
Fcgr3a, FcgammaRIV
246256 6.0 3.9
Tlr2 toll-like receptor 2 Ly105 24088 2.0 1.5
Tlr9 toll-like receptor 9 81897 2.8 2.3
Tlr12 toll-like receptor 12 Gm1365 384059 1.8 2.8
Cd40 CD40 antigen
IGM, p50, Bp50, GP39,
IMD3, TRAP, HIGM1, T- 21939 5.1 2.6 x
BAM, Tnfrsf5
Cd86 CD86 antigen
B7, B70, MB7, B7-2,
B7.2, CLS1, Ly58, ETC-1,
Ly-58, MB7-2, Cd28l2,
12524 6.5 5.4
TS/A-2
Cd274 CD274 antigen
B7-H1, PD-L1, Pdcd1l1,
Pdcd1lg1
60533 4.0 3.0
Pdcd1lg2 programmed cell death 1 ligand 2 Btdc, B7-DC, PD-L2 58205 5.5 8.6
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.
Finally, the expression of mitochondrial superoxide dismutase 2 (Sod2) and glutaredoxin
(Glrx), which are involved in the anti-oxidant defense, was induced. Contrarily, glutathione
S-transferase mu 1 (Gstm1), which is associated to detoxification processes, was repressed.
Furthermore, the induction of lysosomal enzymes cathepsin C and H (Ctsc, Ctsh) was observed.
BMM induced cell adhesion molecules, integrins, and protocadherin (Icam1, Itgal, Itgb7, Pcdh7,
Vcam1) after IFN-γ treatment, whereas they repressed the beta-integrin subunit Itgb3
(Table R.3.9).
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