Inducible nitric oxide synthase deficiency in mice increases resistance to chronic infection with Echinococcus multilocularis
| Autor: | Marianne Stettler, Wen J Dai, Andreas S. Waldvogel, Thomas W. Jungi, Bruno Gottstein |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Lipopolysaccharide
Secondary infection Immunology Nitric Oxide Synthase Type II Stimulation Lymphocyte Activation Nitric Oxide Echinococcus multilocularis Nitric oxide Microbiology Interferon-gamma Mice chemistry.chemical_compound Echinococcosis Concanavalin A Immune Tolerance Splenocyte Animals Immunology and Allergy Cells Cultured Mice Knockout biology Original Articles biology.organism_classification Immunity Innate Echinococcus Mice Inbred C57BL Nitric oxide synthase Chronic infection Liver chemistry Antigens Helminth Chronic Disease biology.protein Female Nitric Oxide Synthase Cell Division Spleen |
| Zdroj: | Immunology. 108:238-244 |
| ISSN: | 1365-2567 0019-2805 |
| DOI: | 10.1046/j.1365-2567.2003.01567.x |
| Popis: | The production of nitric oxide (NO) by intraperitoneal macrophages of mice during secondary infection with Echinococcus multilocularis mediates immunosuppression at early and late stages of infection. We addressed the role of NO in host resistance against this extracellular metazoan parasite by infecting inducible nitric oxide synthase knockout ((iNOS-KO) mice (of the C57BL/6 background) with 100 metacestode vesicles. The parasite weight was significantly lower in iNOS-KO mice when compared with wild-type (WT) mice at 4 months postinfection (late stage), thus demonstrating that iNOS deficiency confers a certain degree of resistance against persistent chronic infection. However, histological analysis of periparasitic tissue showed no differences between WT and iNOS-KO mice, as both exhibited granuloma formation and the presence of giant cells. Together with histology, the production of a high level of interferon-gamma (IFN-gamma) in infected iNOS-KO mice upon stimulation with concanavalin A (Con A) and VF-antigen indicated normal T-cell signalling in these animals. As expected, peritoneal exudate cells (PEC) from infected iNOS-KO mice produced no detectable NO, while the PEC from infected WT mice produced high levels of NO after stimulation with lipopolysaccharide (LPS) and parasite protein or carbohydrate antigen, or even without in vitro stimulation. Consequently, the high level of NO production observed during chronic infection in WT mice appears to contribute more to immunosuppression than to limitation of parasite growth. This is also reflected by the fact that splenocyte proliferation was significantly higher and parasite masses lower in iNOS-KO mice (at 1 and 4 months postinfection) than in WT mice. |
| Databáze: | OpenAIRE |
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