Abstracts (complete list) - Wissenschaft Online

Georg Peschel, Nuria Rodriguez, Christine Cirl, Nina Wantia, Tanja Erl, Susi Dürr,
Hermann Wagner, Thomas Miethke
Chlamydophila pneumoniae follows different strategies to
downregulate surface MHC II expression depending on the
cell type
Chlamydophila pneumoniae (CP), an obligate intracellular bacterium, has developed
several strategies for intracellular survival and to escape from the immune system. One
of the most attractive mechanisms is the downregulation of MHC II in epithelial cells by
degradation of the upstream stimulatory factor-1 (USF-1) by the chlamydial protease
CPAF which is secreted during infection. In WT infected BMDM, where CP does not
replicate as efficient as in epithelial cells, the surface expression of MHC II is
downregulated in comparison with the mock control. Addition of IFNγ one day post
infection did not increase surface MHC II levels compared to IFNγ stimulation alone,
suggesting that infection with CP blocks the stimulatory ability of this cytokine.
However, MyD88 -/- infected BMDM did not show any downregulation of MHC II after
infection, but displayed a substantial upregulation upon infection and subsequent
IFNγ•stimulation. Surprisingly, heat inactivated CP (HI-CP) behaved similar as CP alive.
In addition, RT-PCR to detect CPAF RNA showed no presence of the transcript in WT and
little in MyD88 -/- BMDM, indicating that CPAF may not be involved in MHC II
downregulation in BMDM during infection, but rather a chlamydial PAMP that signals in a
MyD88-dependent manner. By contrary, results obtained from infected WT mouse
embryonic fibroblast (MEFs) showed that HI-CP was not able to impair IFNγ-mediated
MHC II expression. Also, RT-PCR demonstrated the presence of CPAF RNA after
infection and USF-1 was degraded in MEFs after CP infection but not after HI-CP
stimulation. Curiously, USF-1 was upregulated in a MyD88-dependent manner in BMDM
after CP or HI-CP infection, indicating that induction of USF-1 and increased surface
expression of MHC II are not correlated in this cell type. In summary, these data show
that CP prevents IFNγ-induced MHC II upregulation in BMDM via PAMP stimulation
through MyD88-dependent but CPAF-independent mechanism while in MEFs CPAF is
involved and therefore an infection is required.