Inducible nitric oxide synthase deficiency in mice increases resistance to chronic infection with Echinococcus multilocularis.

Dai, Wen J; Waldvogel, Andreas; Jungi, Thomas; Stettler, Marianne; Gottstein, Bruno (2003). Inducible nitric oxide synthase deficiency in mice increases resistance to chronic infection with Echinococcus multilocularis. Immunology, 108(2), pp. 238-244. Wiley-Blackwell

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
UniBE Contributor:	Gottstein, Bruno
Subjects:	600 Technology > 610 Medicine & health 600 Technology > 630 Agriculture
ISSN:	0019-2805
Publisher:	Wiley-Blackwell
Language:	English
Submitter:	Bruno Gottstein
Date Deposited:	23 Jul 2018 08:58
Last Modified:	05 Dec 2022 15:16
PubMed ID:	12562333
URI:	https://boris.unibe.ch/id/eprint/118831