Critical role of TLR2 in triggering protective immunity with cyclophilin entrapped in oligomannose-coated liposomes against Neospora caninum infection in mice. Issue 7 (8th February 2019)

• Record Type: Journal Article
• Authors: Fereig, Ragab M.; Abdelbaky, Hanan H.; Kuroda, Yasuhiro; Nishikawa, Yoshifumi
• Is Part Of: Vaccine. Volume 37:Issue 7(2019)
• Page Start: 937
• Page End: 944
• Publication Date: 2019-02-08
• Subjects: Neospora caninum -- NcCyp -- Vaccination -- Neosporosis -- Cyclophilin; BCA bicinchoninic acid assay -- CCK-8 cell counting kit-8 -- ConA concanavalin A -- DMEM Dulbecco's modified Eagle's medium -- DPI days post-infection -- ELISA enzyme-linked immunosorbent assay -- FBS fetal bovine serum -- HRP horse radish peroxidase -- IFN-γ interferon γ -- IgG immunoglobulin G -- IL-4 interleukin 4 -- PBS phosphate buffered saline -- Nc-1 a strain of Neospora caninum -- NcCyp N. caninum cyclophilin antigen -- NF-κB nuclear factor of kappa B pathway -- OML oligomannose-coated-liposomes -- RPMI-1640 medium Roswell Park Memorial Institute 1640 medium -- TLR2 Toll-like receptor 2; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2019.01.005
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: NcCyp-OML activated NF-κB signaling. NcCyp-OML triggered IL-12p40 production from macrophages. NcCyp-OML induced antigen-specific humoral and cellular immunity. NcCyp-OML protected mice against Neospora infection. TLR2 was required for the protective efficacy induced by NcCyp-OML. Abstract: Neospora caninum is an intracellular protozoan parasite closely related to Toxoplasma gondii. N. caninum is thought to be a major cause of abortion in cattle worldwide. Given the current situation of drastic economic losses and a lack of efficient control strategies against such parasites, the challenge to develop potent vaccine candidates and technologies remains. We investigated the immune stimulating activity of N. caninum cyclophilin (NcCyp) with and without a formulation with oligomannose-coated-liposomes (OML) as the potential adjuvant. NcCyp-OML activated NF-κB in RAW 264.7 cells and triggered interleukin (IL)-12p40 production from murine peritoneal macrophages. In BALB/c mice, immunization with NcCyp-OML was associated with the production of specific antibodies (IgG1 and IgG2a). The specific antibody (IgG1) against naked NcCyp was also observed after the challenge infection, but it was significantly lower than those of NcCyp-OML. Moreover, significant cellular immune responses were induced, including spleen cell proliferation and interferon-gamma production. The immunization of mice with NcCyp-OML, and to lesser extent with naked NcCyp, induced significant protection against challenge with a lethal dose of N. caninum compared with the PBS control group. This protection was associated with a higher survival rate, slight changes in body weight, and lower clinical score of mice. In addition, the significant protective efficacy of NcCyp-OML was confirmed in another mouse strain, male C57BL/6 mice. The current study revealed the marked contribution of Toll-like receptor 2 (TLR2) to the protective immunity triggered by NcCyp-OML because higher numbers of TLR2 −/− mice succumbed to a lethal dose of N. caninum compared with C57BL/6 mice. Moreover, prominent spleen cell proliferation and IFN-γ production was induced in NcCyp-OML-immunized mice by a TLR2-dependent mechanism.