Abstracts (complete list) - Wissenschaft Online

Stella Eugenie Autenrieth, Dirk Middendorf, Ingo Birger Autenrieth
Yersinia enterocolitica induces cell death in splenic dendritic
cells: evidence for YopP dependent and independent
mechanisms
The virulence factor YopP of Yersinia enterocolitica (Ye) induces cell death in mouse
bone marrow-derived dendritic cells (DCs). Here we have investigated whether YopP of
Ye might induce cell death in DCs in vivo. For this purpose, C57BL/6 mice were infected
i.v. with Ye wild type (pYV + ) or with the YopP deficient mutant strain (pYV + ΔyopP).
One, two and three days post infection the number of splenic DCs including
subpopulations as well as the frequency of apoptotic DCs was analyzed by flow
cytometry and immunofluorescence microscopy. Infection of mice with the pYV +
resulted in a higher number of CD11c + cells in the spleen one day post infection
compared to untreated mice. This effect was not observed in the spleen of mice infected
with pYV + ΔyopP, indicating that the rapidly increased number of DCs in the spleen one
day after Yersinia infection is mediated by YopP. Three days post infection the number
of CD11c + cells was three times lower in the spleen of mice infected with pYV +
compared to untreated mice. The decrease in CD11c + cells was associated with
significantly higher numbers of apoptotic and necrotic DCs three days post infection with
the wild type strain pYV + compared to uninfected mice or to mice infected with the YopP
deficient mutant strain pYV + ΔyopP as revealed by immunostaining of active caspase 3,
TUNEL reaction and staining with propidium iodide. However, infection with pYV + ΔyopP
also resulted in a significant, although lower increase of apoptotic DCs suggesting that
part of DC death after Yersinia infection in vivo is caused by mechanisms independent
of YopP. Recent published data suggest, that LPS promotes DC death in bacterial
infections in vivo. Furthermore, analysis of DC subpopulations revealed that Ye induces
cell death predominantly in CD4 + CD8α - DCs. Whether and how this affects priming of T
cells required for the control of Ye infections remains to be shown in future studies.
Taken together, our data demonstrate YopP dependent and YopP independent induction
of DC death in vivo suggesting that YopP, possibly in concert with LPS, induces cell
death in splenic DCs.