Requisite Elements in Vaccine Immunity to Blastomyces dermatitidis: Plasticity Uncovers Vaccine Potential in Immune-Deficient Hosts
| Autor: | Bruce S. Klein, Marcel Wüthrich, Thomas F. Warner, Hanna I. Filutowicz |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Receptors Antigen T-Cell alpha-beta animal diseases T cell Immunology Mice Nude Mice Transgenic chemical and pharmacologic phenomena Nitric Oxide Vaccines Attenuated Blastomycosis Interferon-gamma Mice Immune system Antigen Superoxides T-Lymphocyte Subsets Immunity medicine Animals Immunology and Allergy Fungal vaccine Immunity Cellular Mice Inbred BALB C Attenuated vaccine biology Tumor Necrosis Factor-alpha Blastomyces dermatitidis Immunologic Deficiency Syndromes Th1 Cells biochemical phenomena metabolism and nutrition biology.organism_classification Virology Immunity Innate Mice Inbred C57BL Vaccination medicine.anatomical_structure Blastomyces Cytokines bacteria Fungal Vaccines |
| Zdroj: | The Journal of Immunology. 169:6969-6976 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.169.12.6969 |
| Popis: | Understanding fundamental mechanisms of vaccine immunity will allow proper use and optimization of vaccines. Vaccination with a genetically engineered, live, attenuated strain of Blastomyces dermatitidis carrying a targeted deletion at the BAD1 locus confers sterilizing immunity against experimental lethal pulmonary infection. We found in this study that αβ T cells are requisite for durable vaccine immunity, whereas other T and B cells are dispensable. In immune-competent animals, CD4+ T-cell derived cytokines TNF-α and IFN-γ mediate vaccine immunity. Surprisingly, these factors are dispensable in immune-deficient animals, which rely on alternate mechanisms for robust vaccine immunity, yet still require O2− production rather than generation of NO. Our results clarify the cellular and molecular bases behind the first genetically engineered fungal vaccine. They also illustrate a sharp difference in vaccine mechanisms between immune-competent and immune-deficient hosts, which underscores the plasticity of residual immune elements in compromised hosts, and points to the feasibility of developing vaccines against invasive fungal infection in this fast growing patient population. |
| Databáze: | OpenAIRE |
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