Tailoring host immune responses toListeriaby manipulation of virulence genes – the interface between innate and acquired immunity

Autor: Christian Peters, Martin E. A. Mielke, Abdelhak Darbouche, Eugen Domann, Trinad Chakraborty
Rok vydání: 2003
Předmět:
CD4-Positive T-Lymphocytes
Cytotoxicity
Immunologic
Cellular immunity
CD8-Positive T-Lymphocytes
medicine.disease_cause
Hemolysin Proteins
Mice
T-Lymphocyte Subsets
Immunology and Allergy
Hypersensitivity
Delayed
Listeriosis
Heat-Shock Proteins
Immunity
Cellular
Lymphokines
Virulence
General Medicine
Acquired immune system
Specific Pathogen-Free Organisms
Bacterial vaccine
Infectious Diseases
medicine.anatomical_structure
Bacterial Vaccines
Female
Peptide Termination Factors
Microbiology (medical)
Listeria
T cell
Bacterial Toxins
Immunology
Biology
Vaccines
Attenuated
Microbiology
Lymphocyte Depletion
Interferon-gamma
Immune system
Bacterial Proteins
Species Specificity
Listeria monocytogenes
Immunity
medicine
Animals
RNA
Messenger
Mice
Inbred C57BL
Type C Phospholipases
Trans-Activators
Transformation
Bacterial
Gene Deletion
Spleen
Zdroj: FEMS Immunology & Medical Microbiology. 35:243-253
ISSN: 1574-695X
0928-8244
DOI: 10.1016/s0928-8244(02)00469-8
Popis: Although attenuated strains of microbial pathogens have triggered vaccine development from its origin, the role of virulence factors in determining host immunity has remained largely unexplored. Using the murine listeriosis model, we investigated whether the induction and expansion of protective and inflammatory T cell responses may be modified by selective manipulation of virulence genes. We intentionally deleted specific genes of Listeria monocytogenes, including those encoding the positive regulatory factor (prfA), hemolysin (hly), the actin nucleator (actA), and phospholipase B (plcB). The resulting strains showed decisive differences in their immunogenic properties. In particular, we identified a double-deletion mutant that retained Listeria's profound ability to induce protective CD8(+) T cells, but that is strongly attenuated and exhibits a significantly reduced ability to induce CD4(+) T cell-mediated inflammation. We conclude that this mutant, L. monocytogenes DeltaactADeltaplcB, is at present the most promising mutant for a bacterial vaccine vector and is able to safely induce potent CD8(+) T cell-mediated immunity.
Databáze: OpenAIRE
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