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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
1996-2-14
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pubmed:abstractText |
Production of nitric oxide (NO) by macrophages is important for the killing of intracellular pathogens. IFN-gamma and LPS stimulate NO production by transcriptional up-regulation of inducible nitric oxide synthetase (iNOS). In the present study we used mice with a targeted disruption of the IFN regulatory factor-1 gene (IRF-1-/-) to investigate the importance of NO in the host immune response against Toxoplasma gondii, a major cause of infection in newborns and those with AIDS. IRF-1-/- mice were more susceptible to acute Toxoplasma infection, and treatment with either exogenous IFN-gamma or in vivo neutralization of endogenous IFN-gamma had little effect on their susceptibility to infection. However, administration of exogenous IL-12 was able to prolong survival even when IFN-gamma was depleted. An in vivo depletion study suggested that the mechanism of this protective response is mediated in part by CD4+ T cells. The administration of IL-12 could not overcome the inhibition of lymphoproliferative response in T. gondii-infected mice and treatment with N-monomethyl-L-arginine (L-NMMA), a nitric oxide synthase (iNOS) antagonist in vitro was unable to reverse the immunosuppression. In response to Toxoplasma infection, splenocytes from IRF-1-/- mice exhibited increased production of IL-10 as well as a 30-fold increase in its message expression. These studies indicate that NO may not be essential for host immunity to the parasite, and moreover that IL-12 appears to induce an IFN-gamma-independent mechanism of protection against this opportunistic pathogen.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Immunologic Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-1,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/Irf1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/omega-N-Methylarginine
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
156
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
636-43
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:8543815-Animals,
pubmed-meshheading:8543815-Arginine,
pubmed-meshheading:8543815-CD4-Positive T-Lymphocytes,
pubmed-meshheading:8543815-DNA-Binding Proteins,
pubmed-meshheading:8543815-Female,
pubmed-meshheading:8543815-Genetic Predisposition to Disease,
pubmed-meshheading:8543815-Immunologic Factors,
pubmed-meshheading:8543815-Interferon Regulatory Factor-1,
pubmed-meshheading:8543815-Interferon-gamma,
pubmed-meshheading:8543815-Interleukin-10,
pubmed-meshheading:8543815-Interleukin-12,
pubmed-meshheading:8543815-Lymphocyte Activation,
pubmed-meshheading:8543815-Lymphocyte Depletion,
pubmed-meshheading:8543815-Mice,
pubmed-meshheading:8543815-Mice, Inbred C57BL,
pubmed-meshheading:8543815-Mice, Knockout,
pubmed-meshheading:8543815-Nitric Oxide,
pubmed-meshheading:8543815-Nitric Oxide Synthase,
pubmed-meshheading:8543815-Phosphoproteins,
pubmed-meshheading:8543815-T-Lymphocyte Subsets,
pubmed-meshheading:8543815-Toxoplasma,
pubmed-meshheading:8543815-Toxoplasmosis, Animal,
pubmed-meshheading:8543815-Transforming Growth Factor beta,
pubmed-meshheading:8543815-omega-N-Methylarginine
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pubmed:year |
1996
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pubmed:articleTitle |
Production of nitric oxide (NO) is not essential for protection against acute Toxoplasma gondii infection in IRF-1-/- mice.
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pubmed:affiliation |
Department of Medicine, Dartmouth Medical School, Hanover, NH 03755, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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