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

1 Institute of Medical Microbiology and Hygiene, University of Tübingen, Elfriede-Aulhorn-Straße 6, D-72076 Tübingen, Germany 2 Institute of Microbiology, Czech Academy of Sciences, Videnska 1083, CZ-14220 Prague 4, Czech Republic Correspondence Sabine Gröbner sabine.groebner{at}med.uni-tuebingen.de Received 8 June 2007 Accepted 23 October 2007 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- B) activation. However, as shown by measurement of propidium iodide uptake via disrupted cellular membranes, the preincubation of DC with several NF- B 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- B 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. Abbreviations: CLSM, confocal laser scanning microscopy; DC, dendritic cells; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MKK, MAPK kinase; NF- B, nuclear factor-kappa B; PI, propidium iodide.