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Yersinia YopP-induced apoptotic cell death in murine dendritic cells is partially independent from action of caspases and exhibits necrosis-like features

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Abstract

Yersinia outer protein P (YopP) is a virulence factor of Yersinia enterocolitica that is injected into the cytosol of host cells where it targets MAP kinase kinases (MKKs) and inhibitor of κB kinase (IKK)-β resulting in inhibition of cytokine production as well as induction of apoptosis in murine macrophages and dendritic cells (DC). Here we show that DC death was only partially prevented by the broad spectrum caspase inhibitor zVAD-fmk, indicating simultaneous caspase-dependent and caspase-independent mechanisms of cell death induction by YopP. Microscopic analyses and measurement of cell size demonstrated necrosis-like morphology of caspase-independent cell death. Application of zVAD-fmk prevented cleavage of procaspases and Bid, decrease of the inner transmembrane mitochondrial potential ΔΨm and mitochondrial release of cytochrome c. From these data we conclude that YopP-induced activation of the mitochondrial death pathway is mediated upstream via caspases. In conclusion, our results suggest that YopP simultaneously induces caspase-dependent apoptotic and caspase-independent necrosis-like death in DC. However, it has to be resolved if necrosis-like DC death occurs independently from apoptotic events or as an apoptotic epiphenomenon.

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Authors and Affiliations

  1. Institute of Medical Microbiology and Hygiene, Eberhard-Karls-University of Tübingen, Elfriede-Aulhorn-Str. 6, D-72076, Tübingen, Germany

    Sabine Gröbner, Stella E. Autenrieth, Irena Soldanova, Dani S. J. Gunst, Erwin Bohn, Steffen Müller, Ingo B. Autenrieth & Stefan Borgmann

  2. Department of Dermatology, Eberhard-Karls-University of Tübingen, Liebermeister-Str. 25, D-72076, Tübingen, Germany

    Martin Schaller

  3. Department of Dermatology and Venerology, Laboratory of Experimental Dermatology, Otto-von-Guericke-University of Magdeburg, Universitätsplatz 2, D-39106, Magdeburg, Germany

    Martin Leverkus

  4. Department of Internal Medicine I, Eberhard-Karls-University of Tübingen, Otfried-Müller-Str. 10, D-72076, Tübingen, Germany

    Sebastian Wesselborg

Authors
  1. Sabine Gröbner
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  2. Stella E. Autenrieth
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  3. Irena Soldanova
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  4. Dani S. J. Gunst
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  5. Martin Schaller
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  6. Erwin Bohn
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  7. Steffen Müller
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  8. Martin Leverkus
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  9. Sebastian Wesselborg
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  10. Ingo B. Autenrieth
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  11. Stefan Borgmann
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Correspondence to Sabine Gröbner.

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Gröbner, S., Autenrieth, S.E., Soldanova, I. et al. Yersinia YopP-induced apoptotic cell death in murine dendritic cells is partially independent from action of caspases and exhibits necrosis-like features. Apoptosis 11, 1959–1968 (2006). https://doi.org/10.1007/s10495-006-0189-3

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  • DOI: https://doi.org/10.1007/s10495-006-0189-3

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