Abstract
Toxoplasma gondii releases factors that potently stimulate production of interleukin-12 (IL-12) from dendritic cells (DCs). Purification of this activity showed that cyclophilin-18 (C-18) was its principal component, and antibodies generated against recombinant C-18 inhibited tachyzoite extract-induced synthesis of IL-12. Recombinant C-18 showed high affinity for and triggered cell signaling through CCR5, a chemokine receptor important in parasite-induced IL-12 production by DCs. These findings suggest that the unusual potency of T. gondii in inducing IL-12 from DCs results from its synthesis of a unique chemokine mimic that signals through CCR5. The ability to generate this strong protective response may benefit parasite transmission by preventing the protozoan from overwhelming its intermediate hosts.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Calcium Signaling
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Chemotaxis
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Cyclophilins / genetics
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Cyclophilins / immunology
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Cyclosporine / pharmacology
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DNA, Protozoan / genetics
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Dendritic Cells / immunology*
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Dendritic Cells / physiology
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In Vitro Techniques
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Interleukin-12 / biosynthesis
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Molecular Mimicry
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Molecular Sequence Data
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Protein Structure, Tertiary
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Protozoan Proteins / genetics
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Protozoan Proteins / immunology
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Receptors, CCR5 / chemistry
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Receptors, CCR5 / deficiency
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Receptors, CCR5 / genetics
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Receptors, CCR5 / metabolism*
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Recombinant Proteins / genetics
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Recombinant Proteins / immunology
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Toxoplasma / immunology*
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Toxoplasma / pathogenicity
Substances
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DNA, Protozoan
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Protozoan Proteins
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Receptors, CCR5
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Recombinant Proteins
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Interleukin-12
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Cyclosporine
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Cyclophilins