Abstract
A powerful IFN-gamma response is triggered upon infection with the protozoan parasite, Toxoplasma gondii. Several cell populations, including dendritic cells (DCs), macrophages, and neutrophils, produce IL-12, a key cytokine for IFN-gamma induction. However, it is still unclear which of the above cell populations is its main source. Diphtheria toxin (DT) injection causes transient DC depletion in a transgenic mouse expressing Simian DT receptors under the control of the CD11c promoter, allowing us to investigate the role of DCs in IL-12 production. T. gondii-inoculated DT-treated and control groups were monitored for IL-12 levels and survival. We show in this study that DC depletion abolished IL-12 production and led to mortality. Furthermore, replenishment with wild-type, but not MyD88- or IL-12p35-deficient, DCs rescued IL-12 production, IFN-gamma-induction, and resistance to infection in DC-depleted mice. Taken together, the results presented in this study indicate that DCs constitute the major IL-12-producing cell population in vivo during T. gondii infection.
MeSH terms
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Acute Disease
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Adaptor Proteins, Signal Transducing / deficiency
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Adaptor Proteins, Signal Transducing / genetics
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Adoptive Transfer
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Animals
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Antigens, Protozoan / administration & dosage
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Antigens, Protozoan / immunology
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Cell Death / genetics
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Cell Death / immunology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism*
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Dendritic Cells / transplantation
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Immunity, Innate / genetics
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Immunosuppression Therapy
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Interleukin-12 / antagonists & inhibitors
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Interleukin-12 / biosynthesis*
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Interleukin-12 / deficiency
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Interleukin-12 / genetics
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Interleukin-12 Subunit p35
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Myeloid Differentiation Factor 88
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Protein Subunits / deficiency
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Protein Subunits / genetics
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
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Spleen / transplantation
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Toxoplasma / immunology*
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Toxoplasmosis, Animal / genetics
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Toxoplasmosis, Animal / mortality
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Toxoplasmosis, Animal / pathology
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Toxoplasmosis, Animal / prevention & control*
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, Protozoan
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Interleukin-12 Subunit p35
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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Protein Subunits
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soluble tachyzoite antigen, Toxoplasma gondii
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Interleukin-12