Innate immunity in DNA vaccine with Toxoplasma gondii -heat shock protein 70 gene that induces DC activation and Th1 polarization

• Published in: Vaccine 2011-02, Vol.29 (10), p.1899-1905
• Main Authors: Makino, Masayuki, Uemura, Noriko, Moroda, Masataka, Kikumura, Akitoshi, Piao, Lian-Xun, Mohamed, Rabie M, Aosai, Fumie
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Applied microbiology; Biological and medical sciences; Brain; CD4-Positive T-Lymphocytes - immunology; Cell activation; Cysts; DC vaccine; death; Dendritic cells; Dendritic Cells - immunology; DNA vaccines; Female; Fundamental and applied biological sciences. Psychology; gamma -Interferon; Gene Expression Profiling; Gene targeting; Genes; heat-shock protein 70; Helper cells; hosts; HSP70; HSP70 Heat-Shock Proteins - genetics; HSP70 Heat-Shock Proteins - immunology; Hsp70 protein; Immune system; Immunity; Infections; innate immunity; interferon-gamma; Interferon-gamma - biosynthesis; Interleukin 12; Interleukin 17; Interleukin 4; Interleukin-17 - biosynthesis; Interleukin-4 - biosynthesis; Lymph nodes; Lymph Nodes - immunology; Lymphocytes T; messenger RNA; Mice; Mice, Inbred C57BL; Microbiology; mRNA; MyD88 protein; Parasites; Plasmids; Plasmids - administration & dosage; Polarization; Protozoan Proteins - genetics; Protozoan Proteins - immunology; Protozoan Vaccines - genetics; Protozoan Vaccines - immunology; recombinant vaccines; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Signal transduction; Skin; T.g.HSP70 gene vaccine; Th1 Cells - immunology; Th1 polarization; TLR4 protein; Toll-like receptors; Toxoplasma; Toxoplasma - genetics; Toxoplasma - immunology; Toxoplasma gondii; Toxoplasmosis; Transcription activation; vaccination; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - genetics; Vaccines, DNA - immunology; virulence
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2010.12.118

Abstract Toxoplasma gondii -derived heat shock protein 70 ( T.g. HSP70) is a tachyzoite-specific virulent molecule expressed before the death of hosts. We have already demonstrated the vaccine effects of T.g. HSP70 gene targeting peripheral epidermal or dermal dendritic cells (DC) to limit T. gondii loads in T. gondii -infected mice. In the present study, involvement of innate immunity in T.g. HSP70 gene vaccine-induced Th polarization at draining lymph nodes (dLN) of C57BL/6 (B6) mice and vaccine effects against toxoplasmosis have been evaluated. Compared to the mice unvaccinated or vaccinated with empty plasmid, CD11c+ cells at the dLN from naïve B6 mice expressed prominent IL-12 mRNA after the T.g. HSP70 gene vaccine. Also, CD4+ cells at the dLN from the mice expressed prominent interferon-γ, but not IL-4 or IL-17, mRNA at a maximum level at day 5 following vaccination. Thus, in vivo DC activation and successive early Th1 polarization were induced at the dLN of naïve mice by the T.g. HSP70 gene vaccine. The DC activation and Th1 polarization were observed at the dLN from wild type (WT) and Toll-like receptor (TLR) 2-deficient mice, but not TLR4-deficient mice with B6 background by the vaccine. This T.g. HSP70 gene vaccine-induced DC activation and Th1 polarization were also observed in TRIF-deficient mice, but not MyD88-deficient mice with B6 background indicating the involvement of TLR4/MyD88 signal transduction cascade in the vaccine effects with T.g. HSP70 gene. The T.g. HSP70 gene vaccine (twice at a 2-week interval) has been shown to limit T. gondii loads in the mesenteric LN of WT, TLR2-deficient and TRIF-deficient mice, but neither TLR4-deficient nor MyD88-deficient mice, at an acute phase of toxoplasmosis. The T.g. HSP70 gene vaccine also limited cyst number in the brains of WT, TLR2-deficient and TRIF-deficient mice, but not TLR4-deficient mice at a chronic phase of toxoplasmosis. Thus, innate immunity also has effects on the vaccine with T.g. HSP70 gene against acute and chronic phases of toxoplasmosis.