Antigen-specific CD8(+) T cells fail to respond to Shigella flexneri
| Autor: | Armelle Phalipon, Marcia B. Goldberg, Amy M. Doling, Michael N. Starnbach, Philippe J. Sansonetti, Kara S. Giddings, Stephanie P. Jehl |
|---|---|
| Přispěvatelé: | Department of Microbiology and Molecular Genetics, Harvard Medical School [Boston] (HMS), Pathogénie Microbienne Moléculaire, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), Massachusetts General Hospital [Boston], This work was supported by National Institutes of Health grant AI055962 to M.N.S. and grant AI043562 to M.B.G., We thank C. Parsot, M. Oldstone, and N. Shastri for providing various reagents., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collège de France - Chaire Microbiologie et Maladies infectieuses |
| Rok vydání: | 2011 |
| Předmět: |
MESH: Dysentery
Bacillary MESH: Shigella flexneri Immunology Immunoblotting Epitopes T-Lymphocyte Biology CD8-Positive T-Lymphocytes Lymphocyte Activation Microbiology Epitope Shigella flexneri MESH: Epitopes T-Lymphocyte 03 medical and health sciences Interleukin 21 Mice 0302 clinical medicine Antigen MESH: Mice Inbred C57BL Cytotoxic T cell Animals MESH: Animals IL-2 receptor MESH: Lymphocyte Activation MESH: Mice 030304 developmental biology Dysentery Bacillary 0303 health sciences Antigens Bacterial Host Response and Inflammation MESH: Immunoblotting Acquired immune system biology.organism_classification MESH: CD8-Positive T-Lymphocytes [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Virology 3. Good health Mice Inbred C57BL Infectious Diseases Parasitology MESH: Antigens Bacterial CD8 030215 immunology |
| Zdroj: | Infection and Immunity Infection and Immunity, American Society for Microbiology, 2011, 79 (5), pp.2021-2030. ⟨10.1128/IAI.00939-10⟩ Infection and Immunity, 2011, 79 (5), pp.2021-2030. ⟨10.1128/IAI.00939-10⟩ |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | CD8 + T lymphocytes often play a primary role in adaptive immunity to cytosolic microbial pathogens. Surprisingly, CD8 + T cells are not required for protective immunity to the enteric pathogen Shigella flexneri , despite the ability of Shigella to actively secrete proteins into the host cytoplasm, a location from which antigenic peptides are processed for presentation to CD8 + T cells. To determine why CD8 + T cells fail to play a role in adaptive immunity to S. flexneri , we investigated whether antigen-specific CD8 + T cells are primed during infection but are unable to confer protection or, alternatively, whether T cells fail to be primed. To test whether Shigella is capable of stimulating an antigen-specific CD8 + T-cell response, we created an S. flexneri strain that constitutively secretes a viral CD8 + T-cell epitope via the Shigella type III secretion system and characterized the CD8 + T-cell response to this strain both in mice and in cultured cells. Surprisingly, no T cells specific for the viral epitope were stimulated in mice infected with this strain, and cells infected with the recombinant strain were not targeted by epitope-specific T cells. Additionally, we found that the usually robust T-cell response to antigens artificially introduced into the cytoplasm of cultured cells was significantly reduced when the antigen-presenting cell was infected with Shigella . Collectively, these results suggest that antigen-specific CD8 + T cells are not primed during S. flexneri infection and, as a result, afford little protection to the host during primary or subsequent infection. |
| Databáze: | OpenAIRE |
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