genomewide characterization of host-pathogen interactions by ...

Maren Depke
Results
Gene Expression Pattern of Bone-Marrow Derived Macrophages after Interferon-gamma Treatment
regulatory, anti-apoptotic cytokine with structural similarity to IL-2, and the immune modulators
Tnfsf8 and Tnfsf18, members of the TNF ligand superfamily, were higher expressed in BALB/c
BMM.
Strain differences were observed for the interleukin receptors Il4ra (alpha-chain of IL-4
receptor), Il13ra1 (primary IL-13 binding subunit of the IL-13 receptor), and Il21r (IL-21 receptor).
Il4ra and Il13ra1 are linked, because Il13ra1 builds a receptor complex together with Il4ra. All
three interleukin receptor chains were higher expressed in C57BL/6 BMM (Table R.3.12).
Table R.3.12: Strain differences in gene expression of cytokines and cytokine receptors between BMM of BALB/c and C57BL/6 mice.
Rosetta Resolver Annotation fold change a IFN-γ effect
gene
Entrez
description
alias
name
Gene ID
control IFN-γ BALB/c C57BL/6
Ccl24 chemokine (C-C motif) ligand 24 CKb-6, MPIF-2, Scya24 56221 -2.7 -2.2
Ccr2 chemokine (C-C motif) receptor 2
Ckr2, Ccr2a, Ccr2b,
Ckr2a, Ckr2b, mJe-r, 12772 -2.8 -4.0
Cmkbr2, Cc-ckr-2
Cxcl11 chemokine (C-X-C motif) ligand 11
IP9, H174, ITAC, b-R1,
CXC11, I-TAC, SCYB9B, 56066 -1.0 -7.6 x
Scyb11, betaR1
Cxcl14 chemokine (C-X-C motif) ligand 14
KS1, Kec, BMAC, BRAK,
NJAC, MIP-2g, Scyb14, 57266 -4.0 -6.1
bolekine, MIP2gamma
Cxcr4 chemokine (C-X-C motif) receptor 4
CD184, LESTR, Sdf1r,
Cmkar4, PB-CKR, 12767 -2.1 -2.5 x
PBSF/SDF-1
Il4ra interleukin 4 receptor, alpha Il4r, CD124 16190 2.2 1.7 x x
Il13ra1 interleukin 13 receptor, alpha 1 NR4, Il13ra, CD213a1 16164 1.7 1.4 x x
Il15 interleukin 15 16168 -1.5 -2.0 x
Il21r interleukin 21 receptor NILR 60504 3.3 2.8 x
Tnfsf18
tumor necrosis factor (ligand) superfamily,
member 18
Gitrl 240873 1.0 -3.0 x
Tnfsf8
tumor necrosis factor (ligand) superfamily,
member 8
CD153, Cd30l, CD30LG 21949 -1.8 -5.2
a Fold change values were calculated for the comparison of C57BL/6 BMM with the baseline of BALB/c BMM of mean values from
three biological replicates per group. Positive values indicate higher expression in C57BL/6 BMM than in BALB/c BMM, whereas
negative values indicate higher expression in BALB/c BMM than in C57BL/6 BMM. Differential expression between BMM of the two
strains at the same treatment level (IFN-γ treated or medium control) using statistical testing in combination with an absolute fold
change cutoff of 1.5 is indicated in bold.
Furthermore, four GTPases / GTP binding proteins of the p65 and the Mx families, which were
already observed to be induced by IFN-γ within the data set of BALB/c and C57BL/6 BMM,
exhibited strain differences. Gbp1, Mx1, and Mx2 were higher expressed in BALB/c BMM,
whereas Gbp2 was higher expressed in C57BL/6 BMM.
Complement system components C1qb and C1qc, the receptor for complement factor
fragment C5a, C5ar1, but also the complement factor C1 inhibitor, Serping1, were higher
expressed in C57BL/6 BMM (Table R.3.13).
Other immune function related gene expression differences between BMM of the two strains
were conspicuous, because the genes were clearly affected by IFN-γ treatment. First, MHC genes
of class I (H28, H2-Q6, H2-Q8, H2-T24) and class II (H2-Ea) were higher expressed in BALB/c BMM.
But also H2-Ab1 (class II), H2-K1, and H2-M2 (class I) exhibited strain differences, however, their
expression was higher in C57BL/6 BMM. Second, a group of interferon-inducible genes possessed
differences in their expression between BMM of both strains: Ifi27l2a, Ifi44, Ifi202, Ifi203, Ifih1,
Ifit3, Ifitm3, Irf7, and Isg20. All of them were higher expressed in BALB/c BMM than in C57BL/6
BMM (Table R.3.14).
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