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.
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We thank P. Murphy, E. Berger and H. Golding for suggestions and critical reading of this manuscript.
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Supplementary Fig. 1.
Specificity control for antiserum to C-18. Recombinant C-18 molecule (C), STAg (ST) and the tachyzoite culture supernatant (SN) (1μg/lane) were separated by denaturing gel electrophoresis (4-20% gel) and subsequently transferred to PVDF membranes. The figure shows an immunoblot, using for detection rabbit antisera anti-C-18 (1499) or normal rabbit serum (NRS) at a 1:5,000 dilution. (PDF 669 kb)
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Aliberti, J., Valenzuela, J., Carruthers, V. et al. Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells. Nat Immunol 4, 485–490 (2003). https://doi.org/10.1038/ni915
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DOI: https://doi.org/10.1038/ni915
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