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PMID: 9104813 Published · ppublish English Comparative Study Journal Article

Inducible nitric oxide is essential for host control of persistent but not acute infection with the intracellular pathogen Toxoplasma gondii.

The Journal of experimental medicine ·Vol. 185 ·No. 7 ·1997-04-07 ·Pages 1261-73

Scharton-Kersten TM, Yap G, Magram J, Sher A

Abstract

The induction by IFN-gamma of reactive nitrogen intermediates has been postulated as a major mechanism of host resistance to intracellular pathogens. To formally test this hypothesis in vivo, the course of Toxoplasma gondii infection was assessed in nitric oxide synthase (iNOS)-/- mice. As expected, macrophages from these animals displayed defective microbicidal activity against the parasite in vitro. Nevertheless, in contrast to IFN-gamma-/- or IL-12 p40-/- animals, iNOS-deficient mice survived acute infection and controlled parasite growth at the site of inoculation. This early resistance was ablated by neutralization of IFN-gamma or IL-12 in vivo and markedly diminished by depletion of neutrophils, demonstrating the existence of previously unappreciated NO independent mechanisms operating against the parasite during early infection. By 3-4 wk post infection, however, iNOS knockout mice did succumb to T. gondii. At that stage parasite expansion and pathology were evident in the central nervous system but not the periphery suggesting that the protective role of nitric oxide against this intracellular infection is tissue specific rather than systemic.

MeSH Terms
Acute Disease Animals Ascitic Fluid/immunology Brain/parasitology,pathology Chronic Disease Granulocytes/immunology Immunity, Innate Interferon-gamma/biosynthesis Interleukin-12/biosynthesis Macrophages/parasitology Mice Mice, Inbred C57BL Mice, Knockout Nitric Oxide/biosynthesis Nitric Oxide Synthase/deficiency,genetics Survival Analysis Toxoplasma/growth & development Toxoplasmosis, Animal/immunology,mortality
Chemicals
Interleukin-12 Nitric Oxide Interferon-gamma Nitric Oxide Synthase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Scharton-Kersten T M
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Yap G
Magram J
Sher A
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.185.7.1261
Published
1997-04-07
Pages
1261-73
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2196248
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.185.7.1261 PMC Full Text View journal details
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