Yersinia enterocolitica-mediated translocation of defined fusion proteins to the cytosol of mammalian cells results in peptide-specific MHC class I-restricted antigen presentation

Rüssmann, Holger; Weissmüller, Astrid; Geginat, Gernot; Igwe, Emeka I.; Roggenkamp, Andreas; Bubert, Andreas; Goebel, Werner; Hof, Herbert; Heesemann, Jürgen

doi:10.1002/(sici)1521-4141(200005)30:5<1375::aid-immu1375>3.0.co;2-m

Cited by 40 publications

(43 citation statements)

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“…Thus, it could be possible that processed YopE serves as Ag source for MHC class I presentation. In fact, it has been shown that YopE, which is delivered by the Yersinia TTSS into the cytosol of eukaryotic target cells, can act as carrier molecule for heterologous Ags to be presented in an MHC class I-restricted manner (52). This ability may depend on the successful processing A relatively strong background probably resulting from Ab degradation impedes the detection of YopEubiquitin conjugates with the anti-YopE Ab in the molecular mass ranges below 50 kDa (right panel).…”

Section: Discussionmentioning

confidence: 99%

The Proteasome Pathway Destabilizes Yersinia Outer Protein E and Represses Its Antihost Cell Activities

Ruckdeschel

Pfaffinger

Trülzsch

et al. 2006

The Journal of Immunology

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Pathogenic Yersinia spp. neutralize host defense mechanisms by engaging a type III protein secretion system that translocates several Yersinia outer proteins (Yops) into the host cell. Although the modulation of the cellular responses by individual Yops has been intensively studied, little is known about the fate of the translocated Yops inside the cell. In this study, we investigated involvement of the proteasome, the major nonlysosomal proteolytic system in eukaryotic cells, in Yop destabilization and repression. Our data show that inhibition of the proteasome in Yersinia enterocolitica-infected cells selectively stabilized the level of YopE, but not of YopH or YopP. In addition, YopE was found to be modified by ubiquitination. This suggests that the cytotoxin YopE is physiologically subjected to degradation via the ubiquitin-proteasome pathway inside the host cell. Importantly, the increased levels of YopE upon proteasome inhibition were associated with decreased activity of its cellular target Rac. Thus, the GTPase-down-regulating function of YopE is enhanced when the proteasome is inhibited. The stabilization of YopE by proteasome inhibitor treatment furthermore led to aggravation of the cytotoxic YopE effects on the actin cytoskeleton and on host cell morphology. Together, these data show that the host cell proteasome functions to destabilize and inactivate the Yersinia effector protein YopE. This implies the proteasome as integral part of the cellular host immune response against the immunomodulatory activities of a translocated bacterial virulence protein.

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Section: Discussionmentioning

confidence: 99%

The Proteasome Pathway Destabilizes Yersinia Outer Protein E and Represses Its Antihost Cell Activities

Ruckdeschel

Pfaffinger

Trülzsch

et al. 2006

The Journal of Immunology

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“…Immunization with this mutant results in a strong activation of mucosal immunity and a Yersinia-specific T helper type 1 (TH1) response, which protects against challenge with the wild-type Y. enterocolitica. Recombinant antigens expressed by Y. enterocolitica are presented to CD4 or CD8 T cells, depending on the expression plasmid used (Russmann et al, 2001). This bacterial vector was tested in the mouse model of MVE.…”

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“…YopE is a 25 kDa protein containing an N-terminal secretion domain of 15 amino acids and a translocation domain of 50 amino acids. Plasmid pHR43 (Russmann et al, 2001) carries the genetic information for YopE with a deletion of aa ). This truncated version of YopE lacks part of its translocation domain and is therefore secreted but not translocated into the cytoplasm of eukaryotic cells.…”

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confidence: 99%

“…The detection of expression, secretion and translocation of the hybrid YopE-MV-N (aa 79-161) protein was carried out by Western blotting, as described previously (Russmann et al, 2001). To measure expression of YopE-MV-N (aa 79-161), a lysate from non-cell-associated bacteria was used.…”

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confidence: 99%

“…Cells were lysed and proteins were precipitated in the presence of 10 % TCA (Triton X-100-soluble fraction). Samples were separated by 13 % discontinuous SDS-PAGE and transferred to nitrocellulose membranes as described previously (Russmann et al, 2001). Hybrid YopE-MV-N (aa 79-161) protein was detected by immunoblot analysis by treating the membrane with a polyclonal antibody against YopE (Jacobi et al, 1998) followed by horseradish peroxidaselabelled anti-rabbit antibody.…”

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Oral immunization with recombinant Yersinia enterocolitica expressing a measles virus CD4 T cell epitope protects against measles virus-induced encephalitis

Gundel¹,

Weidinger²,

Meulen³

et al. 2003

Journal of General Virology

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Yersinia Outer Protein E, YopE

Rüssmann

Advances in Experimental Medicine and Biology

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Many Gram-negative pathogens evade the host's immune response by utilizing a specialized protein secretion machinery, known as type III secretion system (TTSS). Virulence factors such as the Yersinia outer protein E (YopE) are delivered directly into the cytosol of target cells in a TTSS-dependent fashion. This unique translocation mechanism can be used by attenuated Salmonella carrier vaccines for the delivery of heterologous antigens fused to YopE into the MHC class I-restricted antigen processing pathway. In orally immunized mice, this novel vaccination strategy results in the induction of pronounced peptide-specific cytotoxic CD8 T cell responses.

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Yersinia enterocolitica-mediated translocation of defined fusion proteins to the cytosol of mammalian cells results in peptide-specific MHC class I-restricted antigen presentation

Cited by 40 publications

References 14 publications

The Proteasome Pathway Destabilizes Yersinia Outer Protein E and Represses Its Antihost Cell Activities

The Proteasome Pathway Destabilizes Yersinia Outer Protein E and Represses Its Antihost Cell Activities

Oral immunization with recombinant Yersinia enterocolitica expressing a measles virus CD4 T cell epitope protects against measles virus-induced encephalitis

Yersinia Outer Protein E, YopE

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