Interaktion von Masernviren mit Dendritischen Zellen - OPUS ...

7 Summary
This study investigates the influence of measles virus (MV) on the expression
and usage of different receptors on dendritic cells (DC) was investigated. For
this dendritic cells were generated in vitro by culturing monocytes in the
presence of IL-4 and GM-CSF. The wildtype virus WTF and the vaccine virus
ED were used for the experiments.
The first part of the study analyses the expression of Chemokine receptor 5
(CCR5) and CCR7 as well as functional consequences for the migration of MV-
infected DC-cultures. The expression of CCR5 depends on the maturation state
of DC; expression of CCR5 on immature DC is downregulated during
maturation, while expression of CCR7 is upregulated. This study shows that the
expression of CCR5 on DC is not influenced by MV-infection, although other
characteristic maturation markers are upregulated. In addition, the expression of
CCR7 could not be detected on DC after infection with MV. Chemotaxis assays
were used to investigate the results of the flowcytometric analysis in more
detail. Despite constant CCR5 expression DC of MV-infected cultures showed
impaired migration towards the CCR5 ligand CCL-3. Migration towards the
CCR7 ligand CCL-19 could not be detected due to the lack of CCR7
expression. Additionally, differences in the chemokine expression pattern
between MV-infected and LPS- or mock-treated DC were observed. Short term
infection of DC-cultures resulted in reduced mRNA and protein production of
CXCL-8 and CCL-20 in DC infected with MV compared to LPS- or mock-treated
cells. The migration of T-cells towards supernatants of MV-infected DC was, as
well, impaired in comparison to migration towards supernatants of LPS-treated
DC.
In the second part of this study identified MV as a ligand for the DC-specific
surface molecule DC-SIGN (dendritic cell-specific intercellular adhesion