Type 1 Interferon (IFNα/β) and Type 2 Nitric Oxide Synthase Regulate the Innate Immune Response to a Protozoan Parasite

Type 2 nitric oxide synthase (NOS2) is required for the Th1-dependent healing of infections with intracellular microbes, including Leishmania major. Here, we demonstrate the expression and define the function of NOS2 during the innate response to L. major. At day 1 of infection, genetic deletion or...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 1998, Vol.8 (1), p.77-87
Main Authors: Diefenbach, Andreas, Schindler, Heike, Donhauser, Norbert, Lorenz, Elke, Laskay, Tamás, MacMicking, John, Röllinghoff, Martin, Gresser, Ion, Bogdan, Christian
Format: Article
Language:English
Subjects:
AIDS/HIV
Animals
Antibodies - pharmacology
Cytokines - biosynthesis
Cytokines - immunology
Cytotoxicity, Immunologic
Down-Regulation
Female
Humans
Interferon Type I - immunology
Interferon-gamma - immunology
Isoenzymes - biosynthesis
Isoenzymes - immunology
Killer Cells, Natural - immunology
Leishmania major
Leishmaniasis, Cutaneous - immunology
Macrophages - enzymology
Macrophages - immunology
Male
Mice
Mice, Inbred C57BL
Nitric Oxide Synthase - biosynthesis
Nitric Oxide Synthase - immunology
Rabbits
Th1 Cells - immunology
Transforming Growth Factor beta - biosynthesis
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Summary:Type 2 nitric oxide synthase (NOS2) is required for the Th1-dependent healing of infections with intracellular microbes, including Leishmania major. Here, we demonstrate the expression and define the function of NOS2 during the innate response to L. major. At day 1 of infection, genetic deletion or functional inactivation of NOS2 abolished the IFNγ and natural killer cell response, increased the expression of TGFβ, and caused parasite spreading from the skin and lymph node to the spleen, liver, bone marrow, and lung. Induction of NOS2 was dependent on IFNα/β. Neutralization of IFNα/β mimicked the phenotype of NOS2 −/− mice. Thus, IFNα/β and NOS2 are critical regulators of the innate response to L. major.
ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(00)80460-4