genomewide characterization of host-pathogen interactions by ...

Maren Depke
Results
Host Cell Gene Expression Pattern in an in vitro Infection Model
Plasminogen activator urokinase (PLAU, −2.0) activates plasmin and therefore leads to anticoagulant
activity. But its proteolytic activity also leads to degradation of extracellular matrix
(Dass et al. 2008). The expression of PLAU was decreased in infected S9 cells. Contrarily,
plasminogen activator urokinase receptor (PLAUR; 4.0), receptor for PLAU, was induced. The
receptor promotes and localizes extracellular protease activity and plasmin formation by PLAU,
but also participates in internalization of complexes between PLAU and its inhibitors (Cubellis et
al. 1990, Dass et al. 2008, Blasi/Sidenius 2009). Plasminogen activator inhibitor-1 (PAI-1) is the
main inhibitor of PLAU, and it was induced in infected S9 cells (SERPINE1; 3.3; Table R.4.9)
In infected S9 cells, induction was observed for mitochondrial superoxide dismutase 2 (SOD2;
2.6), a gene known to be inducible in response to oxidative stress and by inflammatory cytokines
like IL-6 (Dougall/Nick 1991, Miao et al. 2009). Furthermore, thioltransferase glutaredoxin (GLRX;
1.9) and thioredoxin interacting protein (TXNIP; 2.2), which are involved in anti-oxidant defense,
were induced (Table R.4.9).
Four components of the complement system were induced in infected S9 cells at the 6.5 h
time point: complement component 1, r subcomponent-like and s subcomponent (C1RL; 1.7;
C1S; 1.7) of the classical pathway, complement factor B (CFB; 3.1) of the alternative pathway and
complement component 3a receptor 1 (C3AR1; 3.6; Table R.4.9).
Lysosomal enzyme genes of cathepsin S (CTSS; 2.6) and legumain (LGMN; 2.3) and
additionally, lysosomal membrane protein genes LAMP3 (5.7) and LAPTM5 (1.9) were induced.
Table R.4.9: Overview on selected differentially expressed immune defense related genes 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
MX1 myxovirus (influenza virus) resistance 1, interferoninducible
4599 MxA, IFI78 2.2
protein p78 (mouse)
MX2 myxovirus (influenza virus) resistance 2 (mouse) 4600 MXB 1.9
GBP1 guanylate binding protein 1, interferon-inducible, 67kDa 2633 2.6
GBP3 guanylate binding protein 3 2635 2.9
GBP4 guanylate binding protein 4 115361 Mpa2 14.9
GBP5 guanylate binding protein 5 115362 11.1
PROCR protein C receptor, endothelial (EPCR) 10544 EPCR, CCD41, CD201 1.6
ADAM17 ADAM metallopeptidase domain 17 6868 CSVP, TACE, CD156B 1.8
TFPI2 tissue factor pathway inhibitor 2 7980 PP5, REF1 2.2
PLAU plasminogen activator, urokinase 5328 ATF, UPA, URK, u-PA -2.0
PLAUR plasminogen activator, urokinase receptor 5329 CD87, UPAR, URKR 4.0
SERPINE1 serpin peptidase inhibitor, clade E (nexin, plasminogen 5054 PAI, PAI-1, PLANH1 3.3
activator inhibitor type 1), member 1
SOD2 superoxide dismutase 2, mitochondrial 6648 IPO-B, Mn-SOD 2.6
GLRX glutaredoxin (thioltransferase) 2745 GRX, GRX1 1.9
TXNIP thioredoxin interacting protein 10628 TXNIP, THIF, VDUP1 2.2
C1RL complement component 1, r subcomponent-like 51279 1.7
C1S complement component 1, s subcomponent 716 1.7
CFB complement factor B 629 3.1
C3AR1 complement component 3a receptor 1 719 3.6
CTSS cathepsin S 1520 2.6
LGMN legumain 5641 AEP, PRSC1 2.3
LAMP3 lysosomal-associated membrane protein 3 27074 CD208, TSC403 5.7
LAPTM5 lysosomal multispanning membrane protein 5 7805 CLAST6 1.9
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
Several adhesins were induced in S. aureus RN1HG GFP infected S9 cells, like integrins alpha
and beta (ITGA2; 2.9; ITGA5; 2.0; ITGA11; 1.6; ITGB8; 2.6) and their regulator cytohesin 1 (CYTH1;
2.1), protocadherins (PCDH7; 4.1; PCDH17; 2.1) and cadherin CDH8 (1.6). Another cadherin was
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