The antigen-specific response to Toxoplasma gondii profilin, a TLR11/12 ligand, depends on its intrinsic adjuvant properties

• Published in: Medical microbiology and immunology Vol. 205; no. 4; pp. 345 - 352
• Main Authors: Hedhli, Dorsaf, Moiré, Nathalie, Akbar, Haroon, Laurent, Fabrice, Héraut, Bruno, Dimier-Poisson, Isabelle, Mévélec, Marie Noëlle
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2016; Springer Nature B.V; Springer Verlag
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Antigens, Protozoan - immunology; Biomedical and Life Sciences; Biomedicine; Female; Immunization; Immunology; Inflammation; Life Sciences; Ligands; Medical Microbiology; Mice, Inbred CBA; Microbiology and Parasitology; Original Investigation; Profilins - immunology; Th1 Cells - immunology; Th2 Cells - immunology; Toll-Like Receptors - agonists; Toxoplasma - immunology; Toxoplasma gondii; Vaccines; Virology; Immunization; TLR; Profilin; .; Adjuvant properties; T. gondii
• ISSN: 0300-8584; 1432-1831
• DOI: 10.1007/s00430-016-0452-3

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.