Molecular mimicry of a CCR5 binding-domain in the microbial activation of dendritic cells

Julio Alberti (Lead / Corresponding author), Jesus G. Valenzuela, Vern B. Carruthers, Sara Hieny, John Andersen, Hugues Charest, Caetano Reis E Sousa, Alan Fairlamb, Jose M. Ribeiro, Alan Sher

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    183 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)485-490
    Number of pages6
    JournalNature Immunology
    Volume4
    Issue number5
    DOIs
    Publication statusPublished - May 2003

    Keywords

    • IMMUNITY
    • IMMUNOPHILINS
    • INTERLEUKIN-12
    • CHEMOKINE RECEPTOR
    • ANTIGEN
    • MALARIA
    • BIOCHEMICAL-CHARACTERIZATION
    • TOXOPLASMA-GONDII
    • RESISTANCE
    • CYCLOPHILIN

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