Induction of nitric oxide synthase protects against malaria in mice exposed to irradiated Plasmodium berghei infected mosquitoes: involvement of interferon gamma and CD8+ T cells
Autor: | I Schneider, M Slayter, J P Weir, J U Aniagolu, Jennifer J. Raney, F W Klotz, Shawn J. Green, M Goodbary, Matthew C. Seguin |
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Rok vydání: | 1994 |
Předmět: |
Plasmodium berghei
CD8 Antigens T-Lymphocytes medicine.medical_treatment Molecular Sequence Data Immunology Biology Nitric oxide Interferon-gamma Mice chemistry.chemical_compound parasitic diseases medicine Animals Immunology and Allergy Cytotoxic T cell Interferon gamma RNA Messenger Mice Inbred BALB C Base Sequence Articles T lymphocyte biology.organism_classification Virology Molecular biology Malaria Nitric oxide synthase Culicidae Cytokine chemistry Enzyme Induction biology.protein Female Immunization Amino Acid Oxidoreductases Nitric Oxide Synthase CD8 medicine.drug |
Zdroj: | The Journal of Experimental Medicine |
ISSN: | 1540-9538 0022-1007 |
DOI: | 10.1084/jem.180.1.353 |
Popis: | Exposure of BALB/c mice to mosquitoes infected with irradiated Plasmodium berghei confers protective immunity against subsequent sporozoite challenge. Immunized mice challenged with viable sporozoites develop parasitemia when treated orally with substrate inhibitors of nitric oxide synthase (NOS). This suggests that the production of nitric oxide (NO) prevents the development of exoerythrocytic stages of malaria in liver. Liver tissue from immunized mice expressed maximal levels of mRNA for inducible NOS (iNOS) between 12 and 24 h after challenge with sporozoites. Intraperitoneal injection of neutralizing monoclonal antibody against interferon gamma (IFN-gamma) or in vivo depletion of CD8+ T cells, but not CD4+ T cells, at the time of challenge blocked expression of iNOS mRNA and ablated protection in immunized mice. These results show that both CD8+ T cells and IFN-gamma are important components in the regulation of iNOS in liver which contributes to the protective response of mice immunized with irradiated malaria sporozoites. IFN-gamma, likely provided by malaria-specific CD8+ T cells, induces liver cells, hepatocytes and/or Kupffer cells, to produce NO for the destruction of infected hepatocytes or the parasite within these cells. |
Databáze: | OpenAIRE |
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