Differential roles of Yersinia outer protein P-mediated inhibition of nuclear factor-kappa B in the induction of cell death in dendritic cells and macrophages.
Yersinia outer protein P (YopP) induces cell death in macrophages and dendritic cells (DC). In DC this YopP-dependent cell death coincides with the inhibition of nuclear factor-kappa B (NF-kappaB) activation. However, as shown by measurement of propidium iodide uptake via disrupted cellular membranes, the preincubation of DC with several NF-kappaB inhibitors prior to infection with Yersinia did not restore the death-inducing capacity of a YopP-deficient Yersinia mutant. These results suggest that in contrast to macrophages, in DC the YopP-dependent inhibition of NF-kappaB activation is not causative for the induction of cell death. Instead, in DC, the inhibition of mitogen-activated protein kinases (MAPKs), in particular, p38 and c-Jun N-terminal kinase, prior to infection with a YopP-deficient Yersinia mutant substituted the death-inducing capacity of the Yersinia wild-type strain, indicating that the YopP-dependent inhibition of MAPKs mediates Yersinia-induced DC death. The differences between DC and macrophages in the mechanisms of cell death induction by YopP presented herein might be crucial for the function of these antigen-presenting cells.
Adkins
Irena
I
Institute of Microbiology, Czech Academy of Sciences, Videnska 1083, CZ-14220 Prague 4, Czech Republic.|Institute of Medical Microbiology and Hygiene, University of Tübingen, Elfriede-Aulhorn-Straße 6, D-72076 Tübingen, Germany.
Schulz
Sebastian
S
Institute of Medical Microbiology and Hygiene, University of Tübingen, Elfriede-Aulhorn-Straße 6, D-72076 Tübingen, Germany.
Borgmann
Stefan
S
Institute of Medical Microbiology and Hygiene, University of Tübingen, Elfriede-Aulhorn-Straße 6, D-72076 Tübingen, Germany.
Autenrieth
Ingo B
IB
Institute of Medical Microbiology and Hygiene, University of Tübingen, Elfriede-Aulhorn-Straße 6, D-72076 Tübingen, Germany.
Gröbner
Sabine
S
Institute of Medical Microbiology and Hygiene, University of Tübingen, Elfriede-Aulhorn-Straße 6, D-72076 Tübingen, Germany.
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D016923:Cell Death; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000382:microbiology*; D017353:Gene Deletion; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011419:Propidium / Q000378:metabolism; D015008:Yersinia enterocolitica / Q000276:immunology* / Q000472:pathogenicity; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D001426:Bacterial Proteins; D016328:NF-kappa B; C109227:YopP protein, Yersinia; D011419:Propidium; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases