Alternative Endogenous Protein Processing via an Autophagy-Dependent Pathway Compensates for Yersinia -Mediated Inhibition of Endosomal Major Histocompatibility Complex Class II Antigen Presentation
| Autor: | Stefan Jellbauer, Klaus Panthel, Holger Rüssmann, Gernot Geginat, Brigitte Köhn, Hans Wolf-Watz, Sigrid Hoffmann, Sara Garbom, Silke Grauling-Halama, Sebastian E. Winter |
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| Rok vydání: | 2010 |
| Předmět: |
Yersinia Infections
Blotting Western Immunology Antigen presentation Fluorescent Antibody Technique Yersinia pseudotuberculosis Infections Endosomes Yersinia Major histocompatibility complex Microbiology Cell Line MHC class II antigen Mice Antigen MHC class I Autophagy Animals Bacterial Secretion Systems Antigen Presentation biology Antigen processing Macrophages Histocompatibility Antigens Class II Listeriolysin O biology.organism_classification Infectious Diseases Yersinia pseudotuberculosis Microbial Immunity and Vaccines biology.protein Parasitology Bacterial Outer Membrane Proteins |
| Zdroj: | Infection and Immunity. 78:5138-5150 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | Extracellular Yersinia pseudotuberculosis employs a type III secretion system (T3SS) for translocating virulence factors ( Yersinia outer proteins [Yops]) directly into the cytosol of eukaryotic cells. Recently, we used YopE as a carrier molecule for T3SS-dependent secretion and translocation of listeriolysin O (LLO) from Listeria monocytogenes . We demonstrated that translocation of chimeric YopE/LLO into the cytosol of macrophages by Yersinia results in the induction of a codominant antigen-specific CD4 and CD8 T-cell response in orally immunized mice. In this study, we addressed the requirements for processing and major histocompatibility complex (MHC) class II presentation of chimeric YopE proteins translocated into the cytosol of macrophages by the Yersinia T3SS. Our data demonstrate the ability of Yersinia to counteract exogenous MHC class II antigen presentation of secreted hybrid YopE by the action of wild-type YopE and YopH. In the absence of exogenous MHC class II antigen presentation, an alternative pathway was identified for YopE fusion proteins originating in the cytosol. This endogenous antigen-processing pathway was sensitive to inhibitors of phagolysosomal acidification and macroautophagy, but it did not require the function either of the proteasome or of transporters associated with antigen processing. Thus, by an autophagy-dependent mechanism, macrophages are able to compensate for the YopE/YopH-mediated inhibition of the endosomal MHC class II antigen presentation pathway for exogenous antigens. This is the first report demonstrating that autophagy might enable the host to mount an MHC class II-restricted CD4 T-cell response against translocated bacterial virulence factors. We provide critical new insights into the interaction between the mammalian immune system and a human pathogen. |
| Databáze: | OpenAIRE |
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