| Project/Area Number |
17590367
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Parasitology (including Sanitary zoology)
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
AOSAI Fumie Chiba University, Grad.Sch.Med., Associate Professor, 大学院医学研究院, 助教授 (80150316)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
YANO Akihiko Chiba University, Grad. Sch. Med., Professor, 大学院医学研究院, 教授 (20135122)
NOROSE Kazumi Chiba University, Grad. Sch. Med., Research Associate (30156244)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥2,700,000 (Direct Cost: ¥2,700,000)
|
|---|
| Keywords | Toxoplasma gondii / Dendritic Cells / DC vaccine / Toll Like Receptor / MyD88 / TRAM / TRIF / IL-12 / siRNA / TLR / 未熟樹状細胞 / 成熟樹状細胞 / Toll-like receptor / 抗原取り込み / MLR |
|---|
| Research Abstract |
Toxoplasma gondii-derived heat shock protein 70 (T.g.HSP70) is a tachyzoite-specific virulent molecule which expression increases just before the death of hosts possessing the pathogenicities to cause deterioration of the host defense. We cloned T.g.HSP70 and partially succeeded to develop in vivo T. g. HSP70 gene vaccine targeting the Langerhans cells (immature dendritic cells (DCs) of skin) by using the gene-gun.
DC is a professional antigen presenting cell (APC) and DC maturation is essential to induce efficient T cell activation. Therefore, in this research, we investigated the role of T.g.HSP70 on DC maturation in vitro by using recombinant T.g.HSP70, and following results were obtained. (1) immature DC were obtained from bone-marrow cells by culturing with IL-4 and GM-CSF. (2) T.g.HSP70 induced DC maturation as evidenced by an increase in surface expression of MHC class I and II molecules and costimulatory molecules such as CD40, CD80, and CD86. Functionally, decreased phagocytic ability and increased alloreactive T cell stimulatory ability were observed in T.g.HSP70-stimulated DCs. (3) The T.g.HSP70-stimulated DC maturation was demonstrated in WT and Toll-like receptor (TLR) 2-deficient but not TLR4-deficient C57BL/6 mice. Furthermore, DCs from WT and TLR2-deficient but not TLR4-deficient mice produced IL-12 after T.g.HSP70-stimulation. (4) Concerning the downstream of TLR4 molecule, the T.g.HSP70-stimulated DC maturation was demonstrated in MyD88-deficient but not TRIF-deficient mice. Furthermore, T.g.HSP70-stimulated DCs from WT, TLR2-deficient and MyD88-deficient but neither TLR4-deficient nor TRIF-deficient mice expressed IFN-mRNA. These data indicated that T.g.HSP70 stimulates murine DC maturation via TLR4 through the MyD88-independent TRIF-deficient signal transduction cascade.
|
