genomewide characterization of host-pathogen interactions by ...

Maren Depke
Results
Host Cell Gene Expression Pattern in an in vitro Infection Model
differentiation (IL12A), epithelial receptor for the inflammatory cytokine IL-22 (IL22RA1),
scavenger receptor for cytokines (CCRL1), immunomodulatory cytokines (IL28A, IL28B, IL29), and
apoptosis inducers (TNFSF10, TNFSF15), but also anti-apoptotic IL-15 and its receptor IL15RA.
Table R.4.8: Overview on differentially expressed cytokines and receptors in S9 cells 6.5 h after start of infection with S. aureus RN1HG
GFP.
Rosetta Resolver annotation
fold change a
gene
name
description
Entrez
Gene ID
CCL2 chemokine (C-C motif) ligand 2 6347 MCP1 2.8
CCL5 chemokine (C-C motif) ligand 5 6352 RANTES 4.0
CCRL1 chemokine (C-C motif) receptor-like 1 51554 CCR11 2.3
CSF1 colony stimulating factor 1 (macrophage) 1435 MCSF 3.1
CXCL10 chemokine (C-X-C motif) ligand 10 3627 IP-10, INP10, IFI10 28.1
CXCL11 chemokine (C-X-C motif) ligand 11 6373 IP9, I-TAC 7.0
CXCL16 chemokine (C-X-C motif) ligand 16 58191 SR-PSOX 1.8
CXCR4 chemokine (C-X-C motif) receptor 4 7852 CD184, SDF1R, LESTR 1.6
IFNB1 interferon, beta 1, fibroblast 3456 3.6
IL6 interleukin 6 (interferon, beta 2) 3569 HGF,HSF,BSF2,IFNB2 11.9
IL7 interleukin 7 3574 2.0
IL12A interleukin 12A 3592 P35,CLMF,NKSF1 4.0
IL15 interleukin 15 3600 3.4
IL15RA interleukin 15 receptor, alpha 3601 2.1
IL22RA1 interleukin 22 receptor, alpha 1 58985 1.8
IL28A interleukin 28A (interferon, lambda 2) 282616 IFNL2 5.1
IL28B interleukin 28B (interferon, lambda 3) 282617 IFNL3 3.0
IL29 interleukin 29 (interferon, lambda 1) 282618 IFNL1 5.7
TNFSF10 tumor necrosis factor (ligand) superfamily, member 10 8743 TRAIL, TL2, APO2L, CD253 18.5
TNFSF13B tumor necrosis factor (ligand) superfamily, member 13b 10673 DTL, BAFF, BLYS, CD257 2.2
TNFSF15 tumor necrosis factor (ligand) superfamily, member 15 9966 TL1, VEGI 4.6
a Fold change values were calculated for the comparison of infected GFP + S9 cell with the baseline of medium control samples.
alias
6.5 h
Further interesting induced genes included myxovirus (influenza virus) resistance 1 and 2
(interferon-inducible protein p78, MX1; 2.2; MX2; 1.9). These genes code for interferon-induced,
antiviral proteins forming a ring-shaped oligomeric structure, which recognizes and sequesters
viral nucleocapsid proteins (Gao et al. 2010). MX1 and MX2 belong to the same family of
interferon-inducible GTPases as the four guanylate binding proteins 1, 3, 4, 5 (interferoninducible,
67kDa, GBP1; 2.6; GBP2; 2.9; GBP3; 14.9; GBP4; 11.1), which were induced in S9 cells
6.5 h after start of infection with S. aureus RN1HG GFP. These GBPs are involved in immune
defense, probably oligomerize, act antivirally and inhibit cellular proliferation (MacMicking 2004).
The fifth member of the p65 GBP family, GBP6, was not expressed on all 16 arrays in this study
(Table R.4.9).
The endothelial protein C receptor (EPCR; PROCR; 1.6) was also induced in infected S9 cells.
Protein C activation by thrombin/thrombomodulin is enhanced when it is bound to EPRC, and
subsequently, activated protein C can act in an anticoagulant and anti-inflammatory manner. In
inflammation, where coagulation is facilitated by different mechanisms, e. g. via C-reactive
protein CRP, the induction of PROCR might indicate a counterregulatory process (Esmon 2006).
Interestingly, the receptor shedding from the cellular surface is mediated by tumor necrosis
factor-alpha converting enzyme / TACE, alias ADAM metallopeptidase domain 17 / ADAM17 (Qu et
al. 2006), which was also induced in the infected S9 cells (ADAM17; 1.8; Table R.4.9).
Further gene expression changes in infected S9 cells could be assigned to a related
physiological aspect: Tissue factor pathway inhibitor 2 (TFPI2; 2.2) belongs like activated
protein C to the natural anticoagulants (Esmon 2006).
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