Abstract
Agonists that activate Toll-like receptors (TLR) are potential vaccine adjuvants. In particular, Toxoplasma gondii profilin (TgPRF) is recognized by TLR11/12 to generate an inflammatory response. Unlike most TLR ligands, TgPRF is also a protein and can therefore simultaneously induce innate and adaptive immune responses. We found that variations in the conformation of TgPRF can affect its ability to induce a TLR11/12-dependent inflammatory response. The secreted recombinant T. gondii (S2-profilin), produced by Schneider 2 cells, has lost its ability to generate an IL-12 response. Reduction of the intramolecular disulfide bonds in S2-profilin rescued the TLR11/12-dependent IL-12 response. Immunization of mice with reduced S2-profilin induced strong cellular and humoral responses compared to mice immunized with unreduced S2-profilin. A mixed Th1/Th2 response was induced with both S2-profilins. However, a more polarized Th1-type response, which was consistent with the IgG2a-polarized humoral response, was observed with reduced S2-profilin. In conclusion, the intrinsic adjuvant properties of TgPRF had significant consequences on the immune response against TgPRF.
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Acknowledgments
This work was supported by the French Embassy and the French Institute for Cooperation in Tunis, Tunisia, and IFR136 Agents Transmissibles et Infectiologie, INRA, Nouzilly, France. We would like to thank J. Pierre, T. Papin and S. Bigot for their excellent technical assistance. We thank Dr D. Soldati, University of Geneva, Switzerland, for providing rabbit serum raised against T. gondii profilin. We thank Dr D Drocourt, InvivoGen, France, for providing the plasmid pPROMTESTT03hss(Tgondii)vseq. The Toxoplasma gondii cDNA library was obtained through the AIDS Research and Reference Reagent program, Division of AIDS, NIAID, NIH.
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Hedhli, D., Moiré, N., Akbar, H. et al. The antigen-specific response to Toxoplasma gondii profilin, a TLR11/12 ligand, depends on its intrinsic adjuvant properties. Med Microbiol Immunol 205, 345–352 (2016). https://doi.org/10.1007/s00430-016-0452-3
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DOI: https://doi.org/10.1007/s00430-016-0452-3