AttenuatedYersinia pseudotuberculosisCarrier Vaccine for Simultaneous Antigen-Specific CD4 and CD8 T-Cell Induction
| Autor: | Holger Rüssmann, Ulrike Gerdemann, Gernot Geginat, Klaus Panthel, Hans Wolf-Watz, Sara Garbom, Emeka I. Igwe, Jürgen Heesemann |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
CD4-Positive T-Lymphocytes
Recombinant Fusion Proteins Bacterial Toxins Immunology Antigen presentation CD8-Positive T-Lymphocytes Biology Vaccines Attenuated Major histocompatibility complex Microbiology Hemolysin Proteins Mice Antigen MHC class I Animals Cytotoxic T cell Yersinia pseudotuberculosis Listeriosis Heat-Shock Proteins Antigens Bacterial Mice Inbred BALB C Vaccines Synthetic Macrophages Listeriolysin O biology.organism_classification Peptide Fragments Bacterial vaccine Protein Transport Infectious Diseases Bacterial Vaccines Microbial Immunity and Vaccines biology.protein Parasitology Bacterial Outer Membrane Proteins |
| Zdroj: | Infection and Immunity. 71:3463-3472 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | Yersinia pseudotuberculosisemploys a type III secretion system for targeting of several virulence factors directly to the cytosol of eukaryotic cells. This protein translocation mechanism mediates the ability ofYersiniato resist phagocytosis and is required for sustained extracellular bacterial replication. In the present study, theYersiniaouter protein E (YopE) was used as a carrier molecule for type III-dependent secretion and translocation of listeriolysin O (LLO) fromListeria monocytogenes. In comparison to wild-typeYersinia, an attenuatedY.pseudotuberculosis yopK-null mutant strain hypertranslocates chimeric YopE/LLO into the cytosol of macrophages, resulting in enhanced major histocompatibility complex (MHC) class I-restricted antigen presentation of an LLO-derived CD8 T-cell epitope. Remarkably, T-cell activation assays also revealed a superior ability of translocated over secreted LLO to induce MHC class II-restricted antigen presentation. These in vitro observations were confirmed after immunization of mice with a single dose of theyopK-null mutant strain. Animals orally inoculated with recombinantYersiniaexpressing translocated chimeric YopE/LLO revealed high numbers of gamma interferon-producing LLO-specific CD4 and CD8 T cells. For the first time, it is shown that cytosolic antigen display mediated by an extracellular bacterial carrier vaccine results in simultaneous CD4 and CD8 T-cell priming, conferring protection against an intracellular pathogen. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|