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

Med Microbiol Immunol. 2016 Mar 2. [Epub ahead of print]

Hedhli D¹, Moiré N¹, Akbar H¹, Laurent F², Héraut B¹, Dimier-Poisson I¹, Mévélec MN³.

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.

KEYWORDS:

Adjuvant properties; Immunization; Profilin; T. gondii; TLR

PMID:

26935827

[PubMed - as supplied by publisher]