title: The antigen-specific response to Toxoplasma gondii profilin, a TLR11/12 ligand, depends on its intrinsic adjuvant properties.
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.
authors.affiliation: Université de Tours, UMR1282 Infectiologie et Santé Publique, 37000, Tours, France.
authors.forename: Dorsaf
authors.initials: D
authors.lastname: Hedhli
authors.affiliation: Université de Tours, UMR1282 Infectiologie et Santé Publique, 37000, Tours, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Moiré
authors.affiliation: Université de Tours, UMR1282 Infectiologie et Santé Publique, 37000, Tours, France.
authors.forename: Haroon
authors.initials: H
authors.lastname: Akbar
authors.affiliation: INRA, UMR1282 Infectiologie et Santé Publique, 37380, Nouzilly, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Laurent
authors.affiliation: Université de Tours, UMR1282 Infectiologie et Santé Publique, 37000, Tours, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Héraut
authors.affiliation: Université de Tours, UMR1282 Infectiologie et Santé Publique, 37000, Tours, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dimier-Poisson
authors.affiliation: Université de Tours, UMR1282 Infectiologie et Santé Publique, 37000, Tours, France. mevelec@univ-tours.fr.
authors.forename: Marie Noëlle
authors.initials: MN
authors.lastname: Mévélec
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D005260:Female; D008808:Mice, Inbred CBA; D051304:Profilins / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists*; D014122:Toxoplasma / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D051304:Profilins; C482903:Tlr11 protein, mouse; C539092:Tlr12 protein, mouse; D051193:Toll-Like Receptors
keywords: Adjuvant properties; Immunization; Profilin; T. gondii; TLR